THE TOP 5 THINGS YOU MAY HAVE MISSED AT pCR (P = .003).

pCR (P = .003). The 3-year OS rate was also significantly higher in

SABCS patients who achieved pCR with neoadjuvant therapy versus
patients wgo did not reach a pCR (94% vs. 87%, respectively; P =
Wayne Kuznar
.005). In NeoALTTO, dual HER2 blockade with trastuzumab and
lapatinib (Tykerb) was superior to either monotherapy with either
San Antonio, TX—The following are 5 topics that you may have
drug in achieving pCR.
missed from the San Antonio Breast Cancer Symposium, which was
held December 10-14, 2013:
5. An adaptive phase 2 trial design has yielded a drug, veliparib,
for phase 3 testing in the neoadjuvant setting in women with triple-
1. A meta-analysis of individual patient data from 36 randomized
negative breast cancer. Veliparib, a poly ADP ribose polymerase
controlled clinical trials of bisphosphonate therapy in women with
inhibitor, advanced to phase 3 on the basis of \ (Paraplatin) and standard
early breast cancer showed a 17% reduction in the risk of breast
chemotherapy, or twice the pathologic response rate achieved in controls
cancer mortality in estrogen-deprived women, but no effect on this
who were treated with standard neoadjuvant therapy. A total of 38
end point in premenopausal women. The Early Breast Cancer Trialists’
patients with triple-negative cancer were enrolled in this arm of the phase
Collaborative Group conducted the meta-analysis, the findings of which
2 study (1 of 7 experimental treatment arms to be evaluated to date) and
were reported by Rob Coleman, MD, Academic Unit of Clinical Oncology,
were treated for 6 months. In an adaptive design, several drugs can be
Weston Park Hospital, University of Sheffield, United Kingdom. The
studied in small groups of patients, and during the trial patients with
meta-analysis included data from 17,709 women, and the 17% reduction
higher probabilities of response can be assigned to therapies that
in the risk of breast cancer mortality found in estrogen-deprived women
perform better in their subtype of disease, said Hope S. Rugo, MD,
randomized to a bisphosphonate relative to placebo or to open control
Professor of Medicine, and Director of Breast Oncology and Clinical
was highly significant (P = .004).
Trials Education, University of California, San Francisco. On the basis of
2. HER2-positive breast cancer appears to be an this trial, statisticians estimate a 92% Bayesian predictive probability that
immunogenic cancer type, and trastuzumab’s activity in this cancer adding veliparib and carboplatin would be statistically superior to
involves not only the direct killing of tumor cells, but also the relief standard therapy for women with triple-negative breast cancer in a 300-
of suppression of antitumor immunity. The evidence comes from the patient randomized phase 3 clinical trial.
evaluation of lymphocytic infiltration of HER2-positive breast tumors.
Some of these cancers were found to exhibit high levels of tumor-
infiltrating lymphocytes that contain the immunosuppressive genes See more at: http://www.valuebasedcancer.com/article/top-5-things-you-
programmed death 1 and cytotoxic T-lymphocyte–associated may-have-missed-sabcs#sthash.e1VC5yWn.dpuf
protein 4. Women with breast tumors with a high number of tumor-
infiltrating lymphocytes had better outcomes with trastuzumab (Herceptin)
in a retrospective analysis of the FinHer trial, said Sherene Loi, MD,
PhD, a medical oncologist and Head of the Translational Breast Cancer
Genomics Laboratory at the Peter MacCallum Cancer Centre in
Melbourne, Australia.

3. The nonsteroidal aromatase inhibitor anastrozole (Arimidex)

may prevent breast cancer in women at significant risk of the
disease. In the International Breast Cancer Intervention Study II,
3864 postmenopausal women at high risk of developing breast cancer
based on family history were randomly assigned to placebo or to
anastrozole for 5 years. At a median follow-up of 5 years, women
assigned to anastrozole had a 53% reduction in incident breast
cancer compared with women who received placebo, reported Jack
Cuzick, PhD, Head of the Cancer Research Centre for Cancer Prevention
and Director of the Wolfson Institute of Preventive Medicine, Queen Mary
University, London.

4. Pathologic complete response (pCR) predicted “significantly

better event-free survival [EFS] and overall survival [OS] compared
with no pCR” in women with HER2-positive, hormone receptor-
negative breast cancer in a trial known as NeoALTTO, said Martine
Piccart-Gebhart, MD, PhD, Chair of the Breast International Group,
Brussels, Belgium. As a result, pCR might be an appropriate end point for
drug approval by the US Food and Drug Administration. In a 30-week
landmark analysis, the 3-year EFS rate among patients who achieved
a pCR was 86% compared with 72% for patients who did not have a
What's new in oncology
Authors
Don S Dizon, MD, FACP
April F Eichler, MD, MPH
Michael E Ross, MD
Diane MF Savarese, MD
Disclosures
All topics are updated as new evidence becomes available and our peer
review process is complete.
Literature review current through: Dec 2013. | This topic last
updated: Jan 14, 2014.
BREAST CANCER
Breast MRI for patients with high-risk lesions (January 2014)
Breast MRI is not recommended for screening in women at average risk
for breast cancer, and the American Cancer Society does not
recommend MRI screening for women at increased risk for breast cancer
because of a history of lobular carcinoma in situ (LCIS) or atypical
hyperplasia (AH). This position was supported by the analysis of
a database of nearly 800 women with LCIS, in which some women were
screened with MRI in addition to mammography and clinical breast
examinations at the discretion of their provider. At a median follow up 58
months, those screened with MRI had the same crude breast cancer
detection rate (13 percent) as those screened with mammography and
exam alone [1]. MRI was not associated with earlier stage of detection,
smaller tumor size, or node negativity. Thus, routine use of breast MRI for
breast cancer screening in women with LCIS cannot be recommended.
(See "Atypia and lobular carcinoma in situ: High risk lesions of the
breast", section on 'Breast MRI for patients with high-risk lesions'.)
Bisphosphonates for breast cancer metastatic to bones (January
2014)
An osteoclast inhibitor is routinely administered for patients with
metastatic breast cancer (MBC) involving bone. Among available agents,
the bisphosphonates are commonly prescribed. Prior data suggested that
the oral bisphosphonate ibandronate had similar efficacy to the
intravenous formulation, zoledronic acid (ZA). However, in a randomized
trial comparing ZA and ibandronate in patients with MBC and bone
metastases, ibandronate resulted in a significantly higher annual rate of
skeletal related events [2]. While overall toxicity profiles were similar, ZA
was associated with a higher incidence of nephrotoxicity. Although ZA is
more active agent than ibandronate, the oral schedule of ibandronate and
the lower risk of renal toxicity makes ibandronate a reasonable
alternative, wherever it is available. (See "Osteoclast inhibitors in the
management of bone metastases from breast cancer", section on 'Oral
versus IV bisphosphonates'.)
Radiation therapy and implant breast reconstruction (December
2013)
Following mastectomy and implant breast reconstruction, radiation
therapy is associated with an increased risk of implant
complications including fibrosis, capsular constriction, and delayed
wound healing. In a cohort study that included 725 women (754
reconstructed breasts) undergoing breast reconstruction with implants
following mastectomy for cancer, the five-year implant failure rates for
nonradiated implants, implants placed post radiation, and implants placed
prior to radiation were 10.4, 28.2, and 25.2 percent respectively [3]. The
majority of women in all groups would encourage implant reconstruction
for other women. (See "Breast reconstruction in women with breast
cancer", section on 'Impact of RT on implants'.)
Anastrozole for breast cancer prevention (December 2013)
In women at high risk for breast cancer, selective estrogen receptor
modulators (SERMs, tamoxifen or raloxifene) are often prescribed
prophylactically. Data suggest that the aromatase inhibitors (AIs) are
also effective agents. In the International Breast cancer Intervention
Study (IBIS-II) approximately 4000 postmenopausal women at high risk
of breast cancer were randomly assigned to treatment with anastrozole or
placebo for five years [4]. As presented at the 2013 San Antonio Breast
Cancer Symposium, anastrozole significantly reduced the incidence of
both invasive and in situ breast cancer compared to placebo. These
results are similar to previously published results from a randomized trial
that evaluated the AI, exemestane, as chemoprevention. Based on these
data, both the SERMs and the AIs are reasonable options for breast
cancer prevention in high-risk postmenopausal women. (See "Selective
estrogen receptor modulators and aromatase inhibitors for breast cancer
prevention", section on 'Aromatase inhibitors'.)
Exercise for musculoskeletal symptoms associated with aromatase
inhibitors (December 2013)
For women taking an aromatase inhibitor (AI) as adjuvant treatment for
breast cancer, musculoskeletal (MSK) complaints are a major reason for
drug discontinuation. In the Hormones and Physical Exercise (HOPE)
trial, postmenopausal women with AI-associated arthralgias were
randomly assigned to a supervised exercise regimen or to usual
care [5]. As presented at the 2013 San Antonio Breast Cancer
Symposium, women assigned to exercise experienced significant
improvement in their worst pain score and severity level compared with
usual care. Although the optimal treatment for MSK symptoms has not
been established, these results support exercise in the management of
AI-associated MSK complaints. (See "Adjuvant endocrine therapy for
non-metastatic, hormone receptor-positive breast cancer", section on
'Treatment approach'.)
Intraoperative radiation therapy for newly diagnosed breast cancer
(December 2013)
Radiation therapy (RT) is usually recommended for patients with breast
cancer who are felt to be at increased risk of recurrence. Whole breast
radiation (WBRT) is the standard approach. Intraoperative RT (IORT) has
been evaluated as a means to administer RT in a single day. However,
two trials with follow-up of approximately 2.5 and 6.0 years suggest that
IORT, compared to WBRT, results in a significantly higher rate of in-
breast tumor recurrence [6,7]. The impact of IORT on disease-free and
overall survival requires longer follow-up before it can be considered as a
reasonable alternative to WBRT. (See "Adjuvant radiation therapy for
women with newly diagnosed, non-metastatic breast cancer", section on
'Intraoperative radiation therapy'.)
Concurrent trastuzumab and anthracycline in HER-2 positive breast
cancer (November 2013)
For women with HER2-positive breast cancer, whether an anthracycline
administered concurrently with trastuzumab improves cancer outcomes
sufficiently to justify the increased risk of cardiac toxicity has been
unclear. In the American College of Surgeons Oncology Group
(ACOSOG) Z1041 trial, over 280 women were randomly assigned to
treatment with 5-fluourouracil, epirubicin, and cyclophosphamide (FEC)
followed by trastuzumab plus paclitaxel (arm A) or to paclitaxel followed
by FEC and concurrent trastuzumab (arm B) [8]. There was no difference
in the pathologic complete response rate with either treatment. However, Pertuzumab plus trastuzumab and chemotherapy for HER2-positive
more patients treated in arm B experienced a drop in their left ventricular breast cancer (September 2013)
ejection fraction (LVEF) at weeks 12 and 24 compared to those treated in
For women with newly diagnosed HER2-positive breast cancer who are
arm A. These data suggest there is no advantage to concurrent epirubicin
candidates for neoadjuvant chemotherapy, treatment should incorporate
and trastuzumab administration and support sequential therapy.
a HER2-directed agent. Two trials have shown that chemotherapy plus
(See "Neoadjuvant therapy for breast cancer: Rationale, pretreatment
dual HER2-inhibition, using trastuzumab plus pertuzumab, results in a
evaluation, and therapeutic options", section on 'Timing of initiation of
higher pCR rate compared to trastuzumab plus
HER2-directed agents'.)
chemotherapy [13,14]. These results led to conditional approval by the
New ASCO/CAP criteria for HER2 positivity (October 2013) US Food and Drug Administration of pertuzumab in combination with
trastuzumab and chemotherapy for the neoadjuvant treatment of HER2-
Patients with breast cancers that over express human epidermal growth
positive breast cancer in September 2013 [15]. Full approval will be
factor receptor 2 (HER2) are candidates for HER2-directed agents.
based on the results of an ongoing phase III trial to inform the survival
Updated guidelines from the American Society of Clinical Oncology
outcomes of these regimens. (See "Neoadjuvant therapy for breast
(ASCO), in collaboration with the College of American Pathologists
cancer: Rationale, pretreatment evaluation, and therapeutic options",
(CAP), have redefined criteria for HER2 overexpression [9]. A tumor is
section on 'Chemotherapy plus trastuzumab and pertuzumab'.)
now classified as HER2 positive when there is circumferential, complete,
and intense staining of >10 percent of tumor cells rather than >30 percent Adjuvant chemotherapy for non-metastatic breast cancer
used previously. In addition, HER2-positivity by in situ hybridization is (September 2013)
defined by 1) a HER2 to chromosome 17 enucleation
For most women with newly diagnosed non-metastatic breast cancer who
probe (HER2/CEP17) ratio ≥2.0 (previously ≥2.2) or 2) an average copy
are candidates for adjuvant chemotherapy, we administer an
number ≥6 signals/cell (previously >6 signals/cell). Algorithms for HER2
anthracycline- and taxane-containing adjuvant regimen, of
testing are available (algorithm 1 and algorithm 2).
which multiple combinations are available. The National Surgical Breast
For patients who meet the guidelines for HER2 positivity reflected in the and Bowel Project B-38 evaluated several regimens to determine if one
2013 ASCO/CAP guidelines, we recommend treatment that incorporates should be considered standard of care [16]. Almost 5000 women were
a HER2-directed agent. (See "HER2 and predicting response to therapy randomly assigned to treatment with one of three regimens: every two
in breast cancer", section on 'Testing for HER2 expression'.) week (dose-dense) doxorubicin plus cyclophosphamide followed by
paclitaxel (AC-T); dose-dense AC followed by paclitaxel plus
Sequential single agent endocrine therapy for metastatic breast
gemcitabine (AC-TG); or docetaxel, cyclophosphamide, plus
cancer (October 2013)
doxorubicin (TAC). There were no differences in survival outcomes.
Endocrine therapy is the treatment of choice for most patients with However, TAC resulted in significantly more myelosuppression. Based on
metastatic hormone receptor-positive breast cancer. For those who these results, there is no single standard of care treatment; however, we
experience disease progression on an aromatase inhibitor (AI), there prefer AC-T rather than these other combinations because of the reduced
appears to be no benefit to combined endocrine therapy as second-line risk of hematologic toxicity. (See "Adjuvant chemotherapy for hormone
treatment. This was shown in the SoFEA trial, in which over 700 patients receptor-positive or negative, HER2-negative breast cancer", section on
who progressed on a non-steroidal AI were randomly assigned to 'Regimen'.)
treatment with fulvestrant plus placebo, fulvestrant plus re-treatment with
Treatment duration with trastuzumab in the adjuvant setting
a non-steroidal AI (anastrozole), or the steroidal AI, exemestane
(September 2013)
alone [10]. There was no improvement in progression-free survival with
combined endocrine therapy compared to single agent fulvestrant or For patients with newly diagnosed, non-metastatic HER2-positive breast
exemestane. Given the lack of benefit, single agent endocrine therapy is cancer, adjuvant therapy should include the HER2-directed
preferred for patients who progress after first-line endocrine treatment for agent, trastuzumab. The optimal duration of treatment had not been
metastatic breast cancer. (See "Treatment approach to metastatic resolved although trastuzumab has routinely been administered for one
hormone receptor-positive breast cancer: Endocrine therapy", section on year. Final results of the HERA trial support the use of a one-year course
'Fulvestrant'.) of trastuzumab [17]. With eight years of follow-up, there were no
differences in disease-free or overall survival among patients treated with
Prognosis of microinvasive breast carcinoma (October 2013)
two years compared to one year of adjuvant trastuzumab. These results
Patients diagnosed with microinvasive breast carcinoma have an support the use of trastuzumab for one year when administered in the
excellent prognosis, with a five-year overall survival between 97 and 100 adjuvant setting. (See "Adjuvant medical therapy for HER2-positive
percent. Survival seems to be intermediate between pure DCIS and small breast cancer", section on 'Treatment duration'.)
invasive carcinomas, likely closer to that of DCIS. In one series with a
CANCER SCREENING AND PREVENTION
median follow-up of 8.5 years, there was no difference in the recurrence
rate or five-year survival between patients with microinvasion and pure Screening for lung cancer (January 2014)
DCIS [11]. In addition, the risk of local recurrence in patients with
The US Preventive Services Task Force (USPSTF) has revised its
microinvasive disease following either breast conservation therapy or
guidelines for screening for lung cancer, based on a systematic review
mastectomy is low [12]. (See "Microinvasive breast carcinoma", section
and an analysis of the benefits and harms of lung cancer screening
on 'Prognosis'.)
[18,19]. The USPSTF now recommends annual low-dose CT scan for
high-risk adults (30 pack-year smoking history and current smoker or quit
within the past 15 years), aged 55 to 80 years, with discontinuation of
screening once the individual has not smoked for 15 years or has a
limited life expectancy [20]. UpToDate authors support the USPSTF
recommendations. Criteria for screening from several other groups vary
slightly, setting 74 years as the upper age for screening, consistent with
the study population in the National Lung Screening
Trial. (See "Screening for lung cancer", section on 'Recommendations for
screening by expert groups'.)
Screening by fecal occult blood testing and colorectal cancer
mortality (September 2013)
The Minnesota Colon Cancer Control Study reported 30-year follow-up
on a population (33,020 participants) who were assigned to usual care,
annual or biennial screening with guaiac fecal occult blood testing
(gFOBT) [21]. Over the follow-up period, 70.9 percent of participants had
died. Screening reduced mortality from colorectal cancer (CRC), although
had no impact on all-cause mortality. The effectiveness of screening by
gFOBT annually or biennially for 6 or 11 screenings persisted over 30
years, suggesting long-term benefit from polypectomy. Annual screening
reduced colorectal mortality by 32 percent and biennial screening by 22
percent. The CRC mortality reduction was greater in men than in women,
and no benefit was observed for women less than 60 years of age. These
data reflect a compliant population (90 percent of participants completed
at least one stool test, and 83 percent of positive tests were followed up
with colonoscopy) and an older gFOBT test. (See "Tests for screening for
colorectal cancer: Stool tests, radiologic imaging and endoscopy", section
on 'Guaiac-based fecal occult blood test (gFOBT)'.)
Screening by lower GI endoscopy and colorectal cancer mortality
(September 2013)
In 22 years of follow-up data from the Nurses’ Health Study and Health
Professionals Follow-up Study, screening by either sigmoidoscopy or
colonoscopy was associated with a decreased risk for colorectal cancer
mortality [22]. Colonoscopy was associated with a greater decrease than
sigmoidoscopy (hazard ratios 0.32 and 0.59, respectively). Colorectal
cancers that were diagnosed within five years of colonoscopy had a
different molecular profile and were more likely to have CpG island
methylator phenotype (CIMP) and microsatellite instability. (See "Tests
for screening for colorectal cancer: Stool tests, radiologic imaging and
endoscopy", section on 'Evidence of effectiveness'.)
Overall survival with finasteride chemoprevention in the Prostate
Cancer Prevention Trial (August 2013)
Inhibition of 5-alpha reductase blocks production of androgens involved in
prostate cancer pathogenesis and provides the rationale for the use of
finasteride as a chemopreventive agent against prostate cancer. Results
from the Prostate Cancer Prevention Trial (PCPT) found that prophylactic
use of finasteride for seven years significantly decreased the incidence of
prostate cancer compared with placebo [23]. However, the possible
benefit from this decrease was called into question by an increase in the
absolute number and proportion of high-grade prostate cancers.
Additional long-term follow-up of the PCPT confirmed the significant
decrease in the overall incidence of prostate cancer, which was limited
to a reduction in the incidence of low risk disease [24]. Although an
increase in the incidence of high-grade (Gleason score ≥7) prostate
cancer remained, there was no difference between the finasteride and
placebo groups in overall survival at 15 years. (See "Chemoprevention
strategies in prostate cancer", section on 'Finasteride: Prostate Cancer
Prevention Trial'.)
CANCER SURVIVORSHIP
Updated ASCO guidelines for follow-up of colorectal cancer
survivors (November 2013)
In 2013, the American Society of Clinical Oncology (ASCO) updated its
prior 2005 recommendations for follow-up care, surveillance protocols,
and secondary prevention measures for survivors of colorectal
cancer [25], endorsing the previously published recommendations of
Cancer Care Ontario [26]. Important changes included tailoring
surveillance to the individual patient’s risk and functional status,
emphasis on surveillance during the first two to four years following
diagnosis and treatment, specific recommendations for the elements of
surveillance (table 1), and integration of care with the primary care
physician. In addition, there is more emphasis on maintaining a healthy
body weight, being physically active, and eating a healthy diet.
(See "Surveillance after colorectal cancer resection", section on
'Recommendations from major groups'.)
GASTROINTESTINAL CANCER
Nanoparticle albumin-bound (nab)-paclitaxel plus gemcitabine for
advanced pancreatic cancer (October 2013)
Nanoparticle albumin-bound (nab)-paclitaxel in combination with
gemcitabine has been approved in the United States for the first-line
treatment of patients with metastatic adenocarcinoma of the pancreas.
The multinational MPACT trial of 861 patients with previously untreated
metastatic pancreatic adenocarcinoma found that combined nab-
paclitaxel and gemcitabine, compared to gemcitabine alone, was
associated with a higher objective response rate and longer median
overall (8.5 versus 6.7 months) [27]. Grade 3 or 4 adverse events
occurred more often with combined therapy and included neutropenia,
fatigue, diarrhea, and neuropathy. For patients who are willing to sacrifice
some survival benefit for a less toxic regimen, gemcitabine plus nab-
paclitaxel represents an acceptable alternative to short-term infusional
fluorouracil combined with leucovorin, oxaliplatin, and irinotecan
(FOLFIRINOX) for first-line therapy. (See "Chemotherapy for advanced
exocrine pancreatic cancer", section on 'Gemcitabine plus nab-
paclitaxel'.)
Tumor seeding following endoscopic ultrasound-guided fine-needle
aspiration of pancreatic tumors (August 2013)
Endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) can be
used to diagnose pancreatic tumors. A concern with EUS FNA is that
passage of the needle through the bowel wall into the tumor could lead
to transfer of tumor cells to the needle track or peritoneum. However,
tumor involvement of adjacent structures or the peritoneum can also
happen in the absence of instrumentation. Two retrospective studies with
a total of 385 patients found that patients who underwent EUS FNA of
pancreatic tumors had similar rates of subsequent tumor involvement of
the stomach wall or peritoneum compared with patients who did not
undergo sampling (2 to 8 percent versus 4 to 15 percent) [28,29]. The
studies suggest that EUS FNA of pancreatic tumors should not be
avoided because of concern for tumor seeding. (See"Endoscopic
ultrasound-guided fine-needle aspiration biopsy in the gastrointestinal
tract", section on 'Safety'.)
GENITOURINARY ONCOLOGY
European Association of Urology guidelines for advanced prostate
cancer (January 2014)
The European Association of Urology (EAU) has published revised
guidelines for the treatment of advanced prostate cancer [30]. The
recommendations are largely consistent with guidelines from the National
Comprehensive Cancer Network (NCCN), the American Society of
Clinical Oncology (ASCO), and previous recommendations in UpToDate.
(See "Overview of the treatment of disseminated prostate cancer".)
Androgen deprivation therapy plus chemotherapy for the initial
treatment of metastatic prostate cancer (January 2014)
Androgen deprivation therapy (ADT) is the standard of care for the initial
treatment of men with metastatic prostate cancer, and chemotherapy is
reserved for patients who develop castration resistant disease. In
preliminary results of a large cooperative group trial, the combination of
ADT plus docetaxel chemotherapy as initial therapy significantly
improved overall survival compared with ADT alone, with chemotherapy
reserved for development of castration resistant prostate cancer
[31]. These results require confirmation and additional follow-up to define
the role of initial chemohormonal therapy. (See "Initial hormone therapy
for metastatic prostate cancer", section on 'ADT plus chemotherapy'.)
Stereotactic body radiation therapy for localized prostate cancer
(December 2013)
Stereotactic body radiation therapy (SBRT) is a form of hypofractionation
in which the entire dose of radiation is administered with high precision in
one or a very limited number of fractions. In a pooled analysis of results
from two phase 2 studies using SBRT to treat localized low- and
intermediate-risk prostate cancer, the biochemical relapse free survival
rates at five years were 99 and 93 percent respectively [32]. The
American Society for Radiation Oncology (ASTRO) now considers SBRT
an appropriate alternative for carefully selected low- to intermediate-risk
prostate cancer, although longer follow-up will be required to definitively
establish the role of SBRT [33].
This option may be particularly useful for patients who would benefit from
a shortened hypofractionated course of treatment (eg, elderly patients
who have a long commute to the center or a poor support
system). (See "External beam radiation therapy for localized prostate
cancer", section on 'Stereotactic body RT'.)
Pazopanib versus sunitinib in advanced or metastatic renal cell
carcinoma (September 2013)
Inhibition of the vascular endothelial growth factor (VEGF) pathway plays
an important role in the treatment of advanced or metastatic renal cell
carcinoma (RCC). While the VEGF inhibitors pazopanib and sunitinib are
active in this setting, it has been unclear if there is a preferred agent.
Pazopanib and sunitinib as first-line treatment were compared in
a randomized trial that enrolled over 1100 patients with advanced or
metastatic RCC [34]. Although survival outcomes were similarly for both
drugs, pazopanib resulted in better quality of life, including less fatigue.
These results support the use of pazopanib rather than sunitinib in
previously untreated patients with advanced or metastatic RCC,
particularly in those patients concerned about fatigue. (See "Anti-
angiogenic and molecularly targeted therapy for advanced or metastatic
renal cell carcinoma", section on 'Pazopanib versus sunitinib'.)
Individualized treatment for poor-risk, advanced testicular germ cell
tumors (July 2013)
For men with poor-risk, advanced testicular germ cell tumors, primary
treatment consists of a platinum-based combination regimen. While
standard treatment is effective in most men, a subgroup of these
patients faces a higher risk of disease progression. In a trial presented at
the 2013 American Society of Clinical Oncology annual
meeting, investigators evaluated the impact of individualized treatment
based on early tumor marker (eg, human chorionic
gonadotropin and/or alpha-fetoprotein) declines after the first cycle of
standard therapy [35]. Men deemed to have an unfavorable decline
in their tumor markers after the first cycle of bleomycin, etoposide, or
cisplatin (BEP) were randomly assigned to further treatment with BEP or
to an investigational regimen consisting of paclitaxel plus BEP followed
by cisplatin, ifosfamide, and bleomycin. As presented, men treated
with the investigational regimen had a significantly higher rate of
progression-free survival at three years compared to continued treatment
with BEP. However, there was no significant improvement in overall
survival reported. In addition, the investigational treatment resulted in a
higher rate of neurotoxicity. While these results are interesting, we
await longer follow-up from this trial before incorporating this approach
into standard practice. (See "Initial risk-stratified treatment for advanced
testicular germ cell tumors", section on 'Stratified treatment based on
marker decline'.)
GYNECOLOGIC ONCOLOGY
Bevacizumab in first-line treatment of epithelial ovarian cancer
(December 2013)
For patients with newly diagnosed epithelial ovarian cancer (EOC), first-
line treatment consists of a platinum and a taxane. Dose-dense treatment
(carboplatin every three weeks with weekly paclitaxel) improved overall
survival compared to standard therapy (both drugs every three weeks) in
a prior randomized trial. Additional trials suggested that bevacizumab
plus chemotherapy improves progression-free survival. Preliminary data
from a new trial (GOG 262) investigating dose-dense versus standard
therapy, with additional bevacizumab at the choice of the patient, found
no difference in progression-free survival between dose-dense and
standard treatment [36]. Dose-dense treatment did decrease the risk of
disease progression among those patients who did not receive
bevacizumab but not in those who received bevacizumab. We await the
full results of GOG 262 to inform the role of dose-dense chemotherapy
and the impact of bevacizumab on overall survival. (See "First-line
chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian
tubal, and peritoneal cancer", section on 'Conventional versus dose-
dense IV therapy'.)
Cediranib as maintenance treatment for platinum-sensitive recurrent
epithelial ovarian cancer (October 2013)
Women with epithelial ovarian cancer (EOC) who relapse more than six
months from the end of prior treatment have platinum-sensitive recurrent
EOC. Although they usually respond well to chemotherapy, they are at
high risk of another recurrence. Cediranib, an oral angiogenesis inhibitor,
has been evaluated as maintenance treatment in this setting [37]. As
presented at the 2013 European Cancer Congress, maintenance therapy
with cediranib for up to 18 months, compared to placebo, improved
overall survival by two-months but was associated with multiple toxicities,
including hypertension, hemorrhage, and fatigue. Pending publication of
the ICON6 trial to fully inform the outcomes of cediranib in this setting, we
do not currently routinely offer maintenance therapy for these patients,
given the associated toxicities. (See "Medical treatment for relapsed
epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive
disease", section on 'Cediranib'.)
The importance of brachytherapy in the treatment of locally
advanced cervical cancer (July 2013)
Women with locally advanced cervical cancer are generally treated with
concurrent cisplatin plus radiation therapy (RT) utilizing both external
beam RT and vaginal brachytherapy (BT). The importance of BT was
confirmed in a 2013 analysis that included over 7000 women with stage
IB2 to IVA cervical cancer identified in the Surveillance, Epidemiology,
and End Results database [38]. The use of BT resulted in higher rates of
cancer specific and overall survival at four years. Of concern, this
analysis also demonstrated a decreasing trend of utilization of
brachytherapy in the United States during this time, suggesting women
may be undertreated for cervical cancer. Given these data, we
recommend that patients with locally advanced cervical cancer be treated
at centers where the expertise to perform BT
available. (See"Management of locally advanced cervical cancer",
section on 'Role of brachytherapy'.)
Chemoradiation using carboplatin for cervical cancer (July 2013)
For women with locally advanced cervical cancer, chemoradiation using
weekly cisplatin is usually recommended. However, women with chronic
comorbidities (eg, renal failure) are at risk for serious cisplatin-related
toxicities. For these patients, carboplatin is a reasonable substitute for
cisplatin when administered concomitantly with radiation therapy (RT).
This was shown in a prospective study involving over 50 women treated
with carboplatin plus RT [39]. There was no difference in the overall
response rate or survival outcomes at three years when RT was
administered concurrently with carboplatin compared to a historical
control consisting of women treated with cisplatin plus
RT. (See "Management of locally advanced cervical cancer", section on
'Carboplatin'.)
HEAD AND NECK CANCER
Preventing depression in patients with head and neck cancer
(August 2013)
Head and neck cancers are associated with psychiatric complications,
including unipolar major depression and suicide, and observational
studies have suggested that prophylactic treatment may prevent the
onset of depression. A 16-week randomized trail compared escitalopram
with placebo in 125 patients who were about to commence treatment for
newly-diagnosed or recurrent stage II to IV epidermoid cancer of the
head and neck, were not already receiving treatment for depression or
anxiety, and did not meet criteria for major depression [40]. The incidence
of depression (determined by scores on a self-report rating scale) was
lower in patients treated with active drug (10 versus 25 percent).
However, there was a trend for a greater rate of dropout due to adverse
effects of study medication in patients who received escitalopram.
Although it is reasonable to prophylactically prescribe antidepressants for
some patients (eg, those with a prior history of depression), we generally
monitor patients instead, based upon our judgement that additional
studies are needed to confirm these results. (See "Management of
psychiatric disorders in patients with cancer", section on 'Prevention'.)
MELANOMA AND OTHER SKIN CANCER
Trametinib plus dabrafenib for BRAF mutation positive advanced
melanoma (January 2014)
The combination of trametinib plus dabrafenib has now been approved by
the US Food and Drug Administration for patients with metastatic
melanoma that contains a V600 mutation in the BRAF gene. Approval
was based upon a phase II trial in which the combination significantly
improved the objective response rate and progression free survival
compared to treatment with dabrafenib alone [41]. (See "Molecularly
targeted therapy for metastatic melanoma", section on 'Trametinib'.)
Antidepressants as prophylaxis for interferon alfa induced
depression (November 2013)
For patients who are treated with interferon, the common side effect of
depression can be prevented with antidepressants. Randomized trials
have previously yielded conflicting results about the benefits of
prophylactic antidepressants, but meta-analyses have found that
prophylaxis is beneficial. A new analysis of eight trials including nearly
is
600 patients compared antidepressants (selective serotonin reuptake
inhibitors) with placebo for preventing depression in patients who were
about to start interferon for hepatitis C or malignant melanoma [42]. Major
depression was less likely to occur during interferon treatment in patients
who received antidepressants (odds ratio 0.4). (See "Neuropsychiatric
side effects associated with interferon-alfa plus ribavirin therapy:
Treatment and prevention", section on 'When to treat for interferon
psychiatric side effects'.)
Sentinel lymph node biopsy in thin melanomas (November 2013)
Sentinel lymph node biopsy (SLNB) is the standard approach for patients
with melanoma when there is a reasonable risk of regional lymph node
metastasis. A retrospective review of 1250 patients with melanomas less
than 1 mm thick by the Sentinel Lymph Node Working Group found that
thickness ≥0.75 mm was an important independent risk factor for regional
lymph node involvement [43]. Based upon these results, SLNB is
indicated for patients with melanoma ≥0.75 mm thick. SLNB can be
considered for patients with melanomas <0.75 mm thick when associated
with other risk factors (ulceration of the primary tumor, mitotic
rate ≥1/mm2, or lymphovascular invasion), but the ratio of potential harm
to benefit needs careful consideration. (See "Evaluation and treatment of
regional lymph nodes in melanoma", section on 'Patient selection'.)
Vismodegib for advanced basal cell carcinoma (November 2013)
Vismodegib, an agent that blocks the hedgehog signaling pathway, is
approved by the US Food and Drug Administration for the treatment of
advanced basal cell cancers (BCC) that are inappropriate for
radiotherapy or surgery. Initial approval was based upon results from one
observational series. In a larger observational study, providing early drug
access to patients with advanced BCC, objective responses were seen in
46 percent of patients with locally advanced disease and 31 percent of
patients with metastatic BCC followed for six months, with side effects of
muscle spasms, dysgeusia, and alopecia affecting the majority of
patients [44]. (See "Systemic treatment of advanced cutaneous
squamous and basal cell carcinomas", section on 'Basal cell carcinoma:
Vismodegib'.)
Targeted therapy for advanced melanoma containing a KIT mutation
(September 2013)
Patients with advanced melanoma that contains a driver mutation may
derive important clinical benefit when managed with targeted therapy.
Patients with metastatic cutaneous melanoma should have their tumors
assayed for the presence of a V600 BRAF mutation; additionally, acral or
mucosal primary tumors that lack a BRAF mutation should be assessed
for a driver mutation in KIT. KIT inhibitors (eg, imatinib) offer an important
option for patients whose melanoma contains a mutation in this
gene [45]. (See "Mucosal melanoma", section on 'Targeted
therapy' and "Molecularly targeted therapy for metastatic melanoma",
section on 'BRAF inhibition'.)
Society for Immunotherapy of Cancer statement on immunotherapy
in melanoma (September 2013)
The Society for Immunotherapy of Cancer (SITC) conducted a systematic
review of the literature on the role of immunotherapy in the management
of patients with melanoma [46]. The SITC consensus statement, based
on this review and consistent with treatment recommendations in
UpToDate, includes the following:
●For patients with metastatic disease, the consensus statement supports
the role of ipilimumab and high-dose interleukin-2 (IL-2), and offers
guidance on the sequencing of these agents vis a vis each other and
targeted therapy in different patient subsets. (See "Overview of the
management of advanced cutaneous melanoma", section on 'Choice and
sequence of therapy'.)
●For patients with completely resected high-risk melanoma, including
those with resected lymph node metastases, the consensus statement
supports the role of immunotherapy with interferon as an adjuvant.
(See "Adjuvant immunotherapy for melanoma", section on 'Risk
stratification and adjuvant therapy'.)
NEUROONCOLOGY
TP53 mutations in sonic hedgehog (SHH) pathway
medulloblastomas (August 2013)
Medulloblastomas with overactivation of the sonic hedgehog (SHH)
pathway are associated with a generally favorable prognosis, although a
minority of patients with these tumors have been noted to have very poor
outcomes. In a collaborative effort that included molecular analysis of
over 500 tumors, somatic TP53 mutations present in 20 percent of SHH
tumors were associated with significantly worse survival compared with
TP53 wild-type tumors [47]. In many cases, germline mutations in TP53
were also identified, indicative of the Li-Fraumeni cancer predisposition
syndrome. TP53 mutations in medulloblastoma are therefore important
both prognostically and with regard to genetic counseling and screening.
(See "Histopathology and molecular pathogenesis of medulloblastoma",
section on 'SHH pathway'.)
PALLIATIVE AND SUPPORTIVE CARE
Futile therapy in the ICU (November 2013)
In a study of specialists in five intensive care units (ICUs) in a US
academic healthcare system, 20 percent of critically ill patients were
perceived by their ICU physician as receiving therapy that was futile or
probably futile [48]. This is similar to reports from Canada and Europe.
Two-thirds of those perceived as receiving futile therapy died before
hospital discharge and the remaining one-third died in the subsequent six
months or remained in a severely compromised state of health, indicating
that these perceptions were accurate. Care that is perceived to be futile is
associated with significant cost, delayed palliative care to relieve patient
suffering, and physician burnout. Good communication with staff and
family members and conflict resolution remain critical in managing
requests for care that may be futile. (See "Ethics in the intensive care
unit: Responding to requests for futile or potentially inappropriate
therapies", section on 'Prevalence'.)
THORACIC ONCOLOGY
Cetuximab in advanced non-small cell lung cancer (November 2013)
Results from two phase III trials investigating cetuximab in combination
with systemic chemotherapy as initial therapy for advanced non-small cell
lung cancer (NSCLC) were equivocal. In a new phase III trial involving
patients with NSCLC who had progressed on platinum-based
chemotherapy, cetuximab plus single agent pemetrexed or docetaxel did
not improve progression free survival or other efficacy parameters [49].
Furthermore, the combination of cetuximab with chemotherapy was
associated with increased toxicity. Thus, the role for cetuximab in
advanced NSCLC remains unclear and requires further investigation.
(See "Initial systemic chemotherapy for advanced non-small cell lung
cancer without a driver mutation", section on 'Cetuximab plus
chemotherapy'.)
Treatment strategies for unresectable stage III non-small cell lung
cancer (October 2013)
Concurrent chemoradiotherapy using a platinum-based doublet in
conjunction with approximately 60 Gy of radiation therapy (RT) is the
current standard for the treatment of unresectable stage III non-small cell
lung cancer. In the RTOG 0617 phase III trial, patients were randomly
assigned to one of four treatments in a 2 x 2 design: chemotherapy with
or without cetuximab and standard-dose RT (60 Gy/30 daily fractions) or
high-dose RT (74 Gy/37 daily fractions) [50]. Results were presented at
the International Association for the Study of Lung Cancer (IASLC)
meeting. Neither the use of a higher dose of radiation nor the addition of
cetuximab improved overall survival compared with standard dose RT
and concurrent chemotherapy without cetuximab. (See "Management of
stage III non-small cell lung cancer", section on 'Targeted
therapy' and "Management of stage III non-small cell lung cancer",
section on 'Radiation dose'.)
Predictors of malignancy in solitary pulmonary nodules (September
2013)
Several models are used to estimate the probability of malignancy in
solitary pulmonary nodules (SPNs) measuring 8 to 30 mm. Most models
have used chest radiograph features to predict the likelihood of
malignancy in a SPN. However, a new model has been developed for
SPNs found on computed tomography (CT). This model showed
excellent discrimination between benign and malignant SPNs when
applied to approximately 3000 high-risk patients (smokers and ex-
smokers) undergoing screening CT for lung cancer [51]. Predictors of
malignancy included: older age, female sex, family history of lung cancer,
emphysema, larger nodule size, upper lobe location, part-solid
appearance, lower nodule count, and spiculation. Although this model
appears useful for estimating the probability of malignancy for SPNs
found by CT in current or ex-smokers, it requires further validation in this
population, as well as in a low-risk population of nonsmokers before it
can be recommended for general application. (See"Diagnostic evaluation
and management of the solitary pulmonary nodule", section on
'Quantitative models for assessing risk of malignancy'.)
Afatinib for advanced non-small cell lung cancer with a mutation in
the epidermal growth factor receptor (August 2013)
Epidermal growth factor receptor (EGFR) inhibitors are active in patients
with advanced non-small cell lung cancer when the tumor contains an
activating mutation in the EGFR. Afatinib (Gilotrif), an irreversible inhibitor
of EGFR, was approved by the US Food and Drug Administration in July
2013 for use in patients with EGFR-mutation positive advanced lung
cancer. Approval was based upon the results of a phase III clinical trial
that demonstrated a significant prolongation of progression free and
overall survival compared with chemotherapy [52,53]. (See "Systemic
therapy for advanced non-small cell lung cancer with an activating
mutation in the epidermal growth factor receptor", section on 'Afatinib'.)
Erlotinib or temozolomide combined with radiation for brain
metastases in non-small cell lung cancer (July 2013)
In a phase III study that was stopped early due to slow accrual, 126
patients with non-small cell lung cancer and one to three brain
metastases were treated with whole brain radiation therapy (WBRT) plus
stereotactic radiosurgery (SRS), WBRT plus SRS plus temozolomide, or
WBRT plus SRS plus erlotinib [54]. Overall survival was worse in each of
the drug therapy arms compared with radiation alone, and toxicity was
significantly higher in patients who received concurrent drug therapy. The
results of this study and others reinforce that neither erlotinib nor
temozolomide should be routinely combined with WBRT. (See "Systemic
therapy for brain metastases", section on 'Targeted
agents' and "Systemic therapy for brain metastases", section on
'Temozolomide'.)
MISCELLANEOUS TUMORS
Prognosis of HIV-related Kaposi sarcoma in the era of antiretroviral
therapy (January 2014)
The widespread use of combination antiretroviral therapy (ART) has led
to a striking decrease in the incidence of HIV-related Kaposi sarcoma
(KS). The prognosis for HIV infected individuals who develop KS is
favorable. In a consecutive series of 469 patients, those with T0 (table 2)
disease were generally treated with ART alone, while those with the more
advanced T1 disease were treated with ART plus chemotherapy. For
those with T0 disease, the five-year overall survival rate was 92 percent
and for those with T1 disease the five-year overall survival rate was 83
percent [55]. (See "AIDS-related Kaposi sarcoma: Staging and
treatment", section on 'Prognosis'.)
OTHER ONCOLOGY
Hepatitis B reactivation with rituximab and ofatumumab (September
2013)
The US Food and Drug Administration has issued boxed warnings for the
monoclonal anti-CD20 monoclonal antibodies rituximab and ofatumumab
regarding an increased risk of hepatitis B reactivation among patients
positive for hepatitis B surface antigen (HBsAg) or antibodies against
hepatitis B core antigen (anti-HBc) [56]. All patients should be
screened with these tests prior to starting treatment. Patients with
evidence of prior hepatitis B infection should be monitored for clinical and
laboratory signs of reactivation during therapy and for several months
after completion of therapy. Rituximab and ofatumumab should be
discontinued in patients with hepatitis reactivation. (See"Treatment of
relapsed or refractory chronic lymphocytic leukemia", section on
'Ofatumumab' and "Rituximab and other B cell targeted therapies for
rheumatoid arthritis", section on 'Opportunistic infections and viral
reactivation'.)
Increased risk of deep vein thrombosis with peripherally-inserted
central catheters (PICCs) (September 2013)
Peripherally-inserted central catheters (PICCs) have been associated
with a greater risk for deep vein thrombosis compared with centrally-
inserted catheters, although the magnitude of the risk was not well
studied. The first meta-analysis of this association included 11
nonrandomized studies comparing PICCs with centrally-inserted
catheters, and found an increased risk of deep vein thrombosis with
PICCs (odds ratio 2.6) [57]. Risk was highest in critically-ill patients and
those with malignancy. There were no pulmonary embolism events for
comparison. (See "Catheter-induced upper extremity venous
thrombosis", section on 'Central versus peripheral vein insertion'.)
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REFERENCES
1. King TA, Muhsen S, Patil S, et al. Is there a role for routine screening MRI in
women with LCIS? Breast Cancer Res Treat 2013; 142:445.
2. Barrett-Lee P, Casbard A, Abraham J, et al. Oral ibandronic acid versus
intravenous zoledronic acid in treatment of bone metastases from breast
cancer: a randomised, open label, non-inferiority phase 3 trial. Lancet Oncol
2014; 15:114.
3. Eriksson M, Anveden L, Celebioglu F, et al. Radiotherapy in implant-based
immediate breast reconstruction: risk factors, surgical outcomes, and patient-
reported outcome measures in a large Swedish multicenter cohort. Breast
Cancer Res Treat 2013; 142:591.
4. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast
cancer in high-risk postmenopausal women (IBIS-II): an international,
double-blind, randomised placebo-controlled trial. Lancet 2013; Online 12
Dec 2013.
5. Irwin ML, Cartmel B, Gross C, et al. Randomized trial of exercise vs usual
care on aromatase inhibitor-associated arthralgias in women with breast
cancer: The hormones and physical exercise study. San Antonio Breast
Cancer Symposium 2013. Abstract S3-03.
6. Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intraoperative
radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year
results for local control and overall survival from the TARGIT-A randomised
trial. Lancet 2013.
7. Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy
versus external radiotherapy for early breast cancer (ELIOT): a randomised
controlled equivalence trial. Lancet Oncol 2013; 14:1269.
8. Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Fluorouracil, epirubicin, and
cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus
paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as
neoadjuvant treatment for patients with HER2-positive breast cancer
(Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol 2013;
14:1317.
9. Wolff AC, Hammond H, Hicks DG, et al. Recommendations for Human
Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American
Society of Clinical Oncology/College of American Pathologists Clinical
Practice Guideline Update. J Clin Oncol 2013; Online 10/7/2013.
10. Johnston SR, Kilburn LS, Ellis P, et al. Fulvestrant plus anastrozole or
placebo versus exemestane alone after progression on non-steroidal
aromatase inhibitors in postmenopausal patients with hormone-receptor-
positive locally advanced or metastatic breast cancer (SoFEA): a composite,
multicentre, phase 3 randomised trial. Lancet Oncol 2013; 14:989.
11. Sue GR, Lannin DR, Killelea B, Chagpar AB. Predictors of microinvasion and
its prognostic role in ductal carcinoma in situ. Am J Surg 2013; 206:478.
12. Margalit DN, Sreedhara M, Chen YH, et al. Microinvasive breast cancer: ER,
PR, and HER-2/neu status and clinical outcomes after breast-conserving
therapy or mastectomy. Ann Surg Oncol 2013; 20:811.
13. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant
pertuzumab and trastuzumab in women with locally advanced, inflammatory,
or early HER2-positive breast cancer (NeoSphere): a randomised
multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13:25.
14. Schneeweiss A, Chia S, Hickish T, et al. Neoadjuvant Pertuzumab and
Trastuzumab Concurrent or Sequential with an Anthracycline-Containing or
Concurrent with an Anthracycline-Free Standard Regimen: A Randomized
 Phase II Study (TRYPHAENA). Cancer Research 2011; 71(24 42. Sarkar S, Schaefer M. Antidepressant Pretreatment for the Prevention of
Suppl.):Abstract S5-6. Interferon Alfa-Associated Depression: A Systematic Review and Meta-
15. FDA approves pertuzumab for neoadjuvant breast cancer. Analysis. Psychosomatics 2013.
http://view.broadcastemail.asco.org/?j=fe591772706302747617&m=fe53157 43. Han D, Zager JS, Shyr Y, et al. Clinicopathologic Predictors of Sentinel
0776d037a7c1d&ls=fdc815727666007f7113747162&l=fe5a1577726000787c Lymph Node Metastasis in Thin Melanoma. J Clin Oncol 2013.
14&s=fe2b11707661037d7d1074&jb=ffcf14&ju=fe1d1778706d0775721477& 44. Chang AL, Solomon JA, Hainsworth JD, et al. Expanded access study of
et_cid=32576933&et_rid=503570844&linkid=View+as+a+Web+Page&r=0 patients with advanced basal cell carcinoma treated with the Hedgehog
(Accessed on September 30, 2013). pathway inhibitor, vismodegib. J Am Acad Dermatol 2013.
16. Swain SM, Tang G, Geyer CE Jr, et al. Definitive results of a phase III 45. Hodi FS, Corless CL, Giobbie-Hurder A, et al. Imatinib for melanomas
adjuvant trial comparing three chemotherapy regimens in women with harboring mutationally activated or amplified KIT arising on mucosal, acral,
operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol and chronically sun-damaged skin. J Clin Oncol 2013; 31:3182.
2013; 31:3197. 46. Kaufman HL, Kirkwood JM, Hodi FS, et al. The Society for Immunotherapy of
17. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of Cancer consensus statement on tumour immunotherapy for the treatment of
adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open- cutaneous melanoma. Nat Rev Clin Oncol 2013; 10:588.
label, randomised controlled trial. Lancet 2013; 382:1021. 47. Zhukova N, Ramaswamy V, Remke M, et al. Subgroup-specific prognostic
18. Humphrey LL, Deffebach M, Pappas M, et al. Screening for lung cancer with implications of TP53 mutation in medulloblastoma. J Clin Oncol 2013;
low-dose computed tomography: a systematic review to update the US 31:2927.
Preventive services task force recommendation. Ann Intern Med 2013; 48. Huynh TN, Kleerup EC, Wiley JF, et al. The frequency and cost of treatment
159:411. perceived to be futile in critical care. JAMA Intern Med 2013; 173:1887.
19. de Koning HJ, Plevritis S, Hazelton WD, et al. Benefits and Harms of 49. Kim ES, Neubauer M, Cohn A, et al. Docetaxel or pemetrexed with or without
Computed Tomography Lung Cancer Screening Programs for High-Risk cetuximab in recurrent or progressive non-small-cell lung cancer after
Populations. Agency for Healthcare Research and Quality; Rockville, MD, platinum-based therapy: a phase 3, open-label, randomised trial. Lancet
MD 2013. Oncol 2013.
20. U.S. Preventive Services Task Force Recommendation Statement: 50. Bradley J, Masters GA, Hu C, et al. An intergroup randomized phase III
Screening for Lung Cancer comparison of standard-dose (60 Gy) versus high-dose (74 Gy)
http://www.uspreventiveservicestaskforce.org/uspstf13/lungcan/lungcanfinalr chemoradiotherapy (CRT) +/- cetuximab (cetux) for stage III non-small cell
s.htm (Accessed on January 03, 2014). lung cancer (NSCLC): Results on cetux from RTOG 0617 (abstract PL03.05).
21. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening IASLC 15th World Conference on Lung Cancer, 2013.
for colorectal cancer. N Engl J Med 2013; 369:1106. 51. McWilliams A, Tammemagi MC, Mayo JR, et al. Probability of cancer in
22. Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal-cancer incidence pulmonary nodules detected on first screening CT. N Engl J Med 2013;
and mortality after lower endoscopy. N Engl J Med 2013; 369:1095. 369:910.
23. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride 52. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or
on the development of prostate cancer. N Engl J Med 2003; 349:215. cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma
24. Thompson IM Jr, Goodman PJ, Tangen CM, et al. Long-term survival of with EGFR mutations. J Clin Oncol 2013; 31:3327.
participants in the prostate cancer prevention trial. N Engl J Med 2013; 53. Yang JC, Hirsh V, Schuler M, et al.. Symptom Control and Quality of Life in
369:603. LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in
25. Meyerhardt JA, Mangu PB, Flynn PJ, et al. Follow-up care, surveillance Patients With Advanced Lung Adenocarcinoma With EGFR Mutations. J Clin
protocol, and secondary prevention measures for survivors of colorectal Oncol 2013.
cancer: american society of clinical oncology clinical practice guideline 54. Sperduto PW, Wang M, Robins HI, et al. A phase 3 trial of whole brain
endorsement. J Clin Oncol 2013; 31:4465. radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS
26. Earle C, Annis R, Sussman J, et al. Follow-up care, surveillance protocol, with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain
and secondary prevention measures for survivors of colorectal cancer. metastases: Radiation Therapy Oncology Group 0320. Int J Radiat Oncol
Recommendations from cancer Care Ontario (CCO) available online at Biol Phys 2013; 85:1312.
https://www.cancercare.on.ca/cms/one.aspx?objectId=280721&contextId=13 55. Bower M, et al. Prospective Stage-Stratified Approach to AIDS-Related
77 (Accessed on November 22, 2013). Kaposi’s Sarcoma. J Clin Oncol 2013.
27. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic 56. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma
cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369:1691. nMedicalProducts/ucm369846.htm (Accessed on September 26, 2013).
28. Yoon WJ, Daglilar ES, Fernandez-Del Castillo C, et al. Peritoneal seeding in 57. Chopra V, Anand S, Hickner A, et al. Risk of venous thromboembolism
Intraductal Papillary mucinous neoplasm of the pancreas patients who associated with peripherally inserted central catheters: a systematic review
underwent Endoscopic ultrasound-guided fine-needle aspiration: Results of and meta-analysis. Lancet 2013; 382:311.
the PIPE study. Gastrointest Endosc 2013; 77:AB409.
29. Ngamruengphong S, Xu C, Woodward TA, et al. Risk of gastric or peritoneal
recurrence, and long-term outcomes, following pancreatic cancer resection
with preoperative endosonographically guided fine needle aspiration.
Endoscopy 2013; 45:619.
30. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU Guidelines on Prostate
Cancer. Part II: Treatment of Advanced, Relapsing, and Castration-Resistant
Prostate Cancer. Eur Urol 2013.
31. http://www.cancer.gov/newscenter/newsfromnci/2013/E3805 (Accessed on
December 19, 2013).
32. King CR, Freeman D, Kaplan I, et al. Stereotactic body radiotherapy for
localized prostate cancer: Pooled analysis from a multi-institutional
consortium of prospective phase II trials. Radiother Oncol 2013; 109:217.
33. http://www.astro.org/uploadedFiles/Main_Site/Practice_Management/Reimbu
rsement/2013HPcoding%20guidelines_SBRT_Final.pdf (Accessed on
December 10, 2013).
34. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in
metastatic renal-cell carcinoma. N Engl J Med 2013; 369:722.
35. Fizazi K, Pagliaro LC, Flechon A, et al. A phase III trial of personalized
chemotherapy based on serum tumor decline in poor-prognosis germ-cell
tumors: Results of GETUG 13. J Clin Oncol 31, 2013 (suppl; abstr LBA4500).
36. Chan J, Brady M, Penson R, et al. Phase III trial of every-3-weeks paclitaxel
versus dose dense weekly paclitaxel with carboplatin +/- bevacizumab in
epithelial ovarian, peritoneal, fallopian tube cancer: GOG 262
(NCT0116712). Oral presentation at the 2013 European Society of
Gynecological Oncology Annual Meeting, Liverpool.
https://docs.google.com/viewer?url=http%3A%2F%2Fjournals.lww.com%2Fij
gc%2FDocuments%2FESGO%252018%2520Meeting%2520Abstracts%2C
%2520Liverpool.pdf (Accessed on October 23, 2013).
37. Ledermann JA, Perren TJ, Raja FA, et al. Randomised double-blined phase
III trial of cediranib (AZD 2171) in relapsed platinum-sensitive ovarian cancer:
Results of the ICON 6 trial. Late Breaking Abstract. Presented at the
European Cancer Congress, Amsterdam, 2013.
38. Han K, Milosevic M, Fyles A, et al. Trends in the utilization of brachytherapy
in cervical cancer in the United States. Int J Radiat Oncol Biol Phys 2013;
87:111.
39. Nam EJ, Lee M, Yim GW, et al. Comparison of carboplatin- and cisplatin-
based concurrent chemoradiotherapy in locally advanced cervical cancer
patients with morbidity risks. Oncologist 2013; 18:843.
40. Lydiatt WM, Bessette D, Schmid KK, et al. Prevention of depression with
escitalopram in patients undergoing treatment for head and neck cancer:
randomized, double-blind, placebo-controlled clinical trial. JAMA Otolaryngol
Head Neck Surg 2013; 139:678.
41. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204114s001lbl.p
df (Accessed on January 09, 2014).