To gain insight into the prevalence and severity of chemotherapy-induced neuropathy and its influence on health-related quality of life (HRQOL) in a population-based sample of colorectal cancer (CRC) survivors 2 to 11 years after diagnosis.

All alive individuals diagnosed with CRC between 2000 and 2009 as registered by the Dutch population-based Eindhoven Cancer Registry were eligible for participation. Eighty-three percent (n = 1,643) of patients filled out the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy 20.

The five neuropathy subscale–related symptoms that bothered patients with CRC the most during the past week were erectile problems (42% of men), trouble hearing (11%), trouble opening jars or bottles (11%), tingling toes/feet (10%), and trouble walking stairs or standing up (9%). Additionally, patients who received oxaliplatin more often reported tingling (29% v 8%; P = .001), numbness (17% v 5%; P = .005), and aching or burning pain (13% v 6%; P = .03) in toes/feet compared with those not treated with chemotherapy. They also more often reported tingling toes/feet (29% v 14%; P = .0127) compared with those treated with chemotherapy without oxaliplatin. Those with many neuropathy symptoms (eg, upper 10%) reported statistically significant and clinically relevant worse HRQOL scores on all EORTC QLQ-C30 subscales (all P < .01).

Two to 11 years after diagnosis of CRC, neuropathy-related symptoms are still reported, especially sensory symptoms in the lower extremities among those treated with oxaliplatin. Because neuropathy symptoms have a negative influence on HRQOL, these should be screened for and alleviated. Future studies should focus on prevention and relief of chemotherapy-induced neuropathy.

In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT).

In the Acute Lymphoblastic Leukemia–Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10^–3 (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10^–3 (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements.

The probability of event-free survival for patients with MRD ≥ 10^–3 was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10^–3 could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) –ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001).

Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.

The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear.

Eighty patients with CD20⁺ lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39).

Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion.

Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.

To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non–small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2.

In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m²) or CP (area under the curve of 5 and 500 mg/m², respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS).

A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm.

Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.

Although radiation therapy (RT) can palliate symptoms and may prolong life, it is not curative for patients with metastatic lung cancer. We investigated patient expectations about the goals of RT for incurable lung cancers.

The Cancer Care Outcomes Research and Surveillance Consortium enrolled a population- and health system–based cohort of patients diagnosed with lung cancer from 2003 to 2005. We identified patients with stage wet IIIB or IV lung cancer who received RT and answered questions on their expectations about RT. We assessed patient expectations about the goals of RT and identified factors associated with inaccurate beliefs about cure.

In all, 384 patients completed surveys on their expectations about RT. Seventy-eight percent of patients believed that RT was very or somewhat likely to help them live longer, and 67% believed that RT was very or somewhat likely to help them with problems related to their cancer. However, 64% did not understand that RT was not at all likely to cure them. Older patients and nonwhites were more likely to have inaccurate beliefs, and patients whose surveys were completed by surrogates were less likely to have inaccurate beliefs. Ninety-two percent of patients with inaccurate beliefs about cure from RT also had inaccurate beliefs about chemotherapy.

Although patients receiving RT for incurable lung cancer believe it will help them, most do not understand that it is not at all likely to cure their disease. This indicates a need to improve communication regarding the goals and limitations of palliative RT.

Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.

We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.

HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.

HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.

Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities.

We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Patients received imatinib 400 mg once per day or 400 mg twice per day if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening was performed by mass spectroscopy.

Twenty-five patients were enrolled (24 evaluable). Eight patients (33%) had tumors with KIT mutations, 11 (46%) with KIT amplifications, and five (21%) with both. Median follow-up was 10.6 months (range, 3.7 to 27.1 months). Best overall response rate (BORR) was 29% (21% excluding nonconfirmed responses) with a two-stage 95% CI of 13% to 51%. BORR was significantly greater than the hypothesized null of 5% and statistically significantly different by mutation status (7 of 13 or 54% KIT mutated v 0% KIT amplified only). There were no statistical differences in rates of progression or survival by mutation status or by melanoma site. The overall disease control rate was 50% but varied significantly by KIT mutation status (77% mutated v 18% amplified). Four patients harbored pretreatment NRAS mutations, and one patient acquired increased KIT amplification after treatment.

Melanomas that arise on mucosal, acral, or CSD skin should be assessed for KIT mutations. Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib.

Active surveillance (AS) is a treatment option for men with very low–risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low–risk PCa, we evaluated oncologic outcomes of AA men with very low–risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP).

We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low–risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features.

AA men with very low–risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P < .001), positive surgical margins (9.8% v 5.9%; P = .02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P = .03) and pathologic upgrading (OR, 2.26; P = .03).

AA men with very low–risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low–risk PCa should be counseled about increased oncologic risk when deciding among their disease management options.

Little is known about the effects of financial relationships between biomedical researchers and industry (financial conflicts of interest [FCOIs]) on research prominence. We examined the prevalence of FCOIs in oncology and associations between FCOIs and research prominence among abstracts presented at American Society of Clinical Oncology (ASCO) annual meetings.

We analyzed 20,718 abstracts presented at ASCO meetings in 2006 and 2008 to 2011. Measures included the following: financial relationships, peer review score (PRS), and meeting placement prominence (descending order of prominence: plenary session, clinical science symposium, oral presentation, poster discussion, general posters, and publish only).

Of 20,718 abstracts, 36% reported at least one author with an FCOI. The proportion of abstracts with any FCOI increased from 33% in 2006 to 38% in 2011 (P < .001). Abstracts with FCOIs had significantly higher meeting prominence compared with publish only and general poster abstracts. The odds ratios compared with general posters were 7.3 for plenary session, 2.2 for clinical science symposium, 1.9 for oral presentation, and 1.7 for poster discussion (P < .001). Abstracts with FCOIs had significantly better PRSs compared with those without FCOIs. For all abstracts, PRS was 2.76 (95% CI, 2.75 to 2.77) with FCOIs compared with 3.01 (95% CI, 3.001 to 3.02) without FCOIs (P < .001). Omitting publish-only abstracts, PRS was 2.62 (95% CI, 2.61 to 2.63) with FCOIs compared with 2.73 without FCOIs (95% CI, 2.71 to 2.73).

Abstracts with FCOIs had more prominent meeting placement and better PRSs. FCOIs were reported more frequently by year, suggesting an increasing influence of industry on cancer research, greater disclosure, or both.

Few studies have examined psychological adjustment for cancer survivors in late treatment and early survivorship stages. Our study investigated the prevalence and short-term trajectories of anxiety, depression, and comorbid anxiety-depression among adult cancer survivors, and identified the individual, disease, health behavior, psychological, and social predictors of chronic and late psychological morbidity.

A heterogeneous sample of adult cancer survivors was recruited from two state-based cancer registries. A total of 1,154 survivors completed self-report questionnaires at 6 (Time 1) and 12 months (Time 2) postdiagnosis. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale with cases identified by a subscale cutoff score ≥ 8. Logistic regression analyses identified Time 1 characteristics associated with anxiety and/or depression at Time 2.

The point prevalence of anxiety (Time 1, 22%; Time 2, 21%), depression (13% at both timepoints) and comorbid anxiety-depression (9% at both timepoints) was similar at 6 and 12 months postdiagnosis. The most prevalent Time 1 to Time 2 trajectory was noncase for anxiety (70%), depression (82%), and comorbid anxiety-depression (87%). While psychological morbidity at Time 1 was the strongest predictor of psychological morbidity at Time 2, being diagnosed with lung cancer and health risk behaviors (smoking, insufficient physical activity) were also strong predictors.

Targeted psychological screening of vulnerable survivors and early intervention may prevent the onset and/or reduce the severity of psychological morbidity in early survivorship. Trials of risk reduction interventions targeting psychological functioning and health risk behaviors seem warranted.

Previous studies have demonstrated the prognostic importance of the immune microenvironment in follicular lymphoma (FL). To investigate the molecular mechanisms during which tumor-infiltrating T cells (TILs) are altered in the FL microenvironment, we studied highly purified CD4 and CD8 TILs from lymph node biopsies at diagnosis in treatment-naive patients with FL compared with reactive tonsils and the peripheral blood of healthy donors.

Gene expression profiling of highly purified CD4 and CD8 TILs was performed on the Affymetrix platform. Diagnostic tissue microarrays from an independent patient set (n = 172) were used to verify protein expression and analyze any impact of TIL-expressed genes on outcome. Time-lapse imaging was used to assess T-cell motility.

The most upregulated genes in both CD4 and CD8 TILs were PMCH, ETV1, and TNFRSF9. PMCH is not expressed in peripheral blood T cells, but expression is highly induced on culture with FL. Both CD4 and CD8 TILs from patients with FL have significantly impaired motility compared with those of healthy TILs from reactive tonsils and this can be induced on healthy T cells by FL cells. During multivariate analysis, a model incorporating the number and location of T cells expressing PMCH, NAMPT, and ETV1 showed prognostic significance for overall survival and for time to transformation.

We showed altered gene expression in TILs in FL and demonstrated that altering the immune microenvironment in FL affects overall survival and time to transformation in this disease.

Patients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in these patients.

Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months.

Of the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission.

Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.

Significant concerns exist regarding the content and reliability of oncology clinical practice guidelines (CPGs). The Institute of Medicine (IOM) report "Clinical Practice Guidelines We Can Trust" established standards for developing trustworthy CPGs. By using these standards as a benchmark, we sought to evaluate recent oncology guidelines.

CPGs and consensus statements addressing the screening, evaluation, or management of the four leading causes of cancer-related mortality in the United States (lung, breast, prostate, and colorectal cancers) published between January 2005 and December 2010 were identified. A standardized scoring system based on the eight IOM standards was used to critically evaluate the methodology, content, and disclosure policies of CPGs. All CPGs were given two scores; points were awarded for eight standards and 20 subcriteria.

No CPG fully met all the IOM standards. The average overall scores were 2.75 of 8 possible standards and 8.24 of 20 possible subcriteria. Less than half the CPGs were based on a systematic review. Only half the CPG panels addressed conflicts of interest. Most did not comply with standards for inclusion of patient and public involvement in the development or review process, nor did they specify their process for updating. CPGs were most consistent with IOM standards for transparency, articulation of recommendations, and use of external review.

The vast majority of oncology CPGs fail to meet the IOM standards for trustworthy guidelines. On the basis of these results, there is still much to be done to make guidelines as methodologically sound and evidence-based as possible.

Prior studies report that half of patients with lung cancer do not receive guideline-concordant care. With data from a national Veterans Health Administration (VHA) study on quality of care, we sought to determine what proportion of patients refused or had a contraindication to recommended lung cancer therapy.

Through medical record abstraction, we evaluated adherence to six quality indicators addressing lung cancer–directed therapy for patients diagnosed within the VHA during 2007 and calculated the proportion of patients receiving, refusing, or having contraindications to recommended treatment.

Mean age of the predominantly male population was 67.7 years (standard deviation, 9.4 years), and 15% were black. Adherence to quality indicators ranged from 81% for adjuvant chemotherapy to 98% for curative resection; however, many patients met quality indicator criteria without actually receiving recommended therapy by having a refusal (0% to 14%) or contraindication (1% to 30%) documented. Less than 1% of patients refused palliative chemotherapy. Black patients were more likely to refuse or bear a contraindication to surgery even when controlling for comorbidity; race was not associated with refusals or contraindications to other treatments.

Refusals and contraindications are common and may account for previously demonstrated low rates of recommended lung cancer therapy performance at the VHA. Racial disparities in treatment may be explained, in part, by such factors. These results sound a cautionary note for quality measurement that depends on data that do not reflect patient preference or contraindications in conditions where such considerations are important.

Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death. No prior studies have adequately controlled for human epidermal growth factor receptor 2 (HER2) status or anti-HER2 treatment. We sought to evaluate whether age was a prognostic or predictive factor in the HERA trial.

We used 2-year median follow-up data and dichotomized age at 40 years to evaluate its prognostic effect on outcomes for women assigned to trastuzumab for 1 year or observation.

Of the 1,703 women randomly assigned to 1 year of trastuzumab and 1,698 to observation, 722 (21%) were age ≤ 40 years at study entry. In separate Cox models, controlling for relevant prognostic and predictive factors, disease-free (DFS) and overall survival (OS) hazard ratios (HRs) were consistent for women age ≤ 40 versus > 40 years, regardless of treatment assignment (observation group: DFS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.90 to 1.54; OS HR age ≤ 40 v > 40 years, 1.01; 95% CI, 0.60 to 1.69; trastuzumab group: DFS HR age ≤ 40 v > 40 years, 1.11; 95% CI, 0.81 to 1.51; OS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.66 to 2.09). Interaction between age group and treatment effect was not statistically significant (DFS P = .89; OS P = .55).

In a retrospective analysis of a large randomized controlled trial of women with early-stage HER2-positive breast cancer, age was not strongly associated with risk of early recurrence or prediction of benefit from trastuzumab therapy. Future research should investigate whether age is a predictor of later recurrence and evaluate the impact of age within groups with other tumor subtypes.