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Journal of Clinical Oncology

Journal of Clinical Oncology RSS feed - Early Release
Journal of Clinical Oncology


Purpose

To evaluate the career plans, professional expectations, and well-being of oncology fellows compared with actual experiences of practicing oncologists.

Methods

US oncology fellows taking the 2013 Medical Oncology In-Training Examination (MedOnc ITE) were invited to participate in an optional postexamination survey. The survey evaluated fellows’ career plans and professional expectations and measured burnout, quality of life (QOL), fatigue, and satisfaction with work-life balance (WLB) using standardized instruments. Fellows’ professional expectations and well-being were compared with actual experiences of US oncologists assessed simultaneously.

Results

Of the 1,637 oncology fellows in the United States, 1,373 (83.9%) took the 2013 MedOnc ITE. Among these, 1,345 (97.9%) completed the postexamination survey. The frequency of burnout among fellows decreased from 43.3% in year 1 to 31.7% in year 2 and 28.1% in year 3 (P < .001). Overall, the rate of burnout among fellows and practicing oncologists was similar (34.1% v 33.7%; P = .86). With respect to other dimensions of well-being, practicing oncologists had lower fatigue (P < .001) and better overall QOL scores (P < .001) than fellows but were less satisfied with WLB (P = .0031) and specialty choice (P < .001). Fellows’ expectations regarding future work hours were 5 to 6 hours per week fewer than oncologists’ actual reported work hours. Levels of burnout (P = .02) and educational debt (P ≤ .004) were inversely associated with ITE scores. Fellows with greater educational debt were more likely to pursue private practice and less likely to plan an academic career.

Conclusion

Oncology fellows entering practice trade one set of challenges for another. Unrealized expectations regarding work hours may contribute to future professional dissatisfaction, burnout, and challenges with WLB.




Purpose

BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL) subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated with risk-directed therapy based on minimal residual disease (MRD) levels during remission induction.

Patients and Methods

Among 422 patients with B-ALL enrolled onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples for gene expression profiling. Next-generation sequencing and/or analysis of genes known to be altered in B-ALL were performed in patients with BCR-ABL1–like ALL who had available material. Outcome was compared between patients with and those without BCR-ABL1–like ALL.

Results

Forty (11.6%) of the 344 patients had BCR-ABL1–like ALL. They were significantly more likely to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction than did other patients with B-ALL. Among 25 patients comprehensively studied for genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and seven had mutations involving the Ras signaling pathway. There were no significant differences in event-free survival (90.0% ± 4.7% [SE] v 88.4% ± 1.9% at 5 years; P = .41) or in overall survival (92.5% ± 4.2% v 95.1% ± 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1–like ALL.

Conclusion

Patients who have BCR-ABL1– like ALL with poor initial treatment response can be salvaged with MRD-based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies.


Purpose

This study evaluated the efficacy of a cancer genetics–specific questionnaire in facilitating communication about, awareness of, and management of psychosocial problems, as well as in lowering distress levels.

Methods

Individuals referred to genetic counseling for cancer at two family cancer clinics in the Netherlands were randomly assigned to an intervention or a control group. All participants completed the psychosocial questionnaire before counseling. In the intervention group, the counselors received the results of this questionnaire before the counseling session. All sessions were audiotaped for content analysis. Primary outcomes were the frequency with which psychosocial problems were discussed, the genetic counselors’ awareness of these problems, and their management. Secondary outcomes included cancer worries and psychological distress, duration and dynamics of the counseling, and satisfaction.

Results

The frequency with which psychosocial problems were discussed with 246 participating counselees was significantly higher in the intervention group (n = 127) than in the control group (n = 119; P = .004), as was the counselors’ awareness of psychosocial problems regarding hereditary predisposition (P < .001), living with cancer (P = .01), and general emotions (P < .001). Counselors initiated more discussion of psychosocial problems in the intervention group (P < .001), without affecting the length of the counseling session. No significant differences were found on management (P = .19). The intervention group reported significantly lower levels of cancer worries (P = .005) and distress (P = .02) after counseling.

Conclusion

The routine assessment of psychosocial problems by questionnaire facilitates genetic counselors’ recognition and discussion of their clients’ psychosocial problems and reduces clients’ distress levels.


Purpose

Chemoimmunotherapy has been the standard of care for chronic lymphocytic leukemia (CLL). However, the introduction of B-cell receptor (BCR) kinase inhibitors such as ibrutinib has the potential to eliminate the role of chemotherapy in the treatment of CLL. How to best incorporate old and new therapies for CLL in this landscape is increasingly complex.

Methods

This article reviews current data available to clinicians and integrates these data to provide a strategy that can be used to approach the treatment of CLL in the era of BCR signaling inhibitors.

Results

Current strategies separate patients based on age or functional status as well as genetics [presence or absence of del(17)(p13.1)]. In the era of targeted therapy, this will likely continue based on current available data. Phase III studies support chemoimmunotherapy as the initial standard therapy for patients without del(17)(p13.1). Choice of chemotherapy (fludarabine plus cyclophosphamide, bendamustine, or chlorambucil) and anti-CD20 antibody (rituximab, ofatumumab, or obinutuzumab) varies based on regimen and patient status. For patients with del(17)(p13.1), no standard initial therapy exists, although several options supported by phase II clinical trials (methylprednisolone plus alemtuzumab or ibrutinib) seem better than chemoimmunotherapy. Treatment of relapsed CLL seems to be best supported by ibrutinib-based therapy. Completion of trials with ibrutinib and other new agents in the near future will offer opportunity for chemotherapy-free treatment across all groups of CLL.

Conclusion

Therapy for CLL has evolved significantly over the past decade with introduction of targeted therapy for CLL. This has the potential to completely transform how CLL is treated in the future.


Gene expression profiling has reshaped our understanding of breast cancer by defining and characterizing four main intrinsic molecular subtypes: human epidermal growth factor receptor 2–enriched, basal-like, luminal A, and luminal B subtypes. Luminal B breast cancer has been reported to have lower expression of hormone receptors, higher expression of proliferation markers, and higher histologic grade than luminal A. It also exhibits worse prognosis and has a distinct profile of response to hormone therapy and chemotherapy. Although luminal cancers share similarities, the studies conducted in recent years using next-generation sequencing technology show that luminal A and B breast cancers should be perceived as distinct entities, with specific oncogenic drivers, rather than more proliferative varieties of luminal tumors. This review discusses the definition and molecular characterization of luminal B breast cancer and presents the available clinical evidence for chemotherapy and endocrine therapy patterns of response. It also provides an overview of ongoing research on molecularly targeted agents for this disease.


Purpose

A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma.

Patients and Methods

RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety.

Results

Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively).

Conclusion

Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.


Purpose

Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease.

Patients and Methods

Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS).

Results

A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival.

Conclusion

IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN.


Purpose

Renal impairment is highly prevalent among patients with cancer, and many patients have undiagnosed chronic kidney disease (CKD) from underlying disease, treatment, or both. African American individuals have disproportionate risk factors (diabetes, hypertension) predisposing them to CKD. We investigated whether African American patients are more likely than white patients to receive morphine with 3- and 6-glucuronide metabolites, which are known to be neurotoxic and accumulate in CKD; whether insurance type mediates the relationship between race and the prescriber’s opioid selection; and whether the chosen opioid has a resultant negative effect according to race.

Patients and Methods

Patients (N = 182) were recruited from oncology clinics within the University of Pennsylvania Health System. Inclusion was based on self-identified African American or white race, age older than 18 years, and the presence of cancer-related pain plus a prescription for morphine or oxycodone. Kidney function was estimated using the abbreviated Modification of Diet in Renal Disease formula.

Results

Patients with CKD who received morphine reported a greater severity of analgesic-related adverse effects than patients with CKD who received oxycodone (P = .010). Controlling for health insurance type, African American patients had 71% lower odds of receiving a prescription of oxycodone than white patients (P < .001). Limiting analysis to those with CKD, the effect of private insurance became insignificant. However, race still remained a significant predictor of the prescribed opioid selection. Race was a strong predictor of adverse effect severity in the presence of CKD, and the type of opioid selection partially mediated this relationship.

Conclusion

Reducing racial disparities in the type of opioid prescription and understanding mechanisms of disproportionate opioid-related adverse effects in African American patients might decrease the clinical disparities in cancer pain outcomes.







Purpose

To investigate the prognostic value of the BRAF V600E mutation and the recently identified TERT promoter mutation chr5:1,295,228C>T (C228T), individually and in their coexistence, in papillary thyroid cancer (PTC).

Patients and Methods

We performed a retrospective study of the relationship of BRAF and TERT C228T mutations with clinicopathologic outcomes of PTC in 507 patients (365 women and 142 men) age 45.9 ± 14.0 years (mean ± SD) with a median follow-up of 24 months (interquartile range, 8 to 78 months).

Results

Coexisting BRAF V600E and TERT C228T mutations were more commonly associated with high-risk clinicopathologic characteristics of PTC than they were individually. Tumor recurrence rates were 25.8% (50 of 194;77.60 recurrences per 1,000 person-years; 95% CI, 58.81 to 102.38) versus 9.6% (30 of 313; 22.88 recurrences per 1,000 person-years; 95% CI, 16.00 to 32.72) in BRAF mutation–positive versus –negative patients (hazard ratio [HR], 3.22; 95% CI, 2.05 to 5.07) and 47.5% (29 of 61; 108.55 recurrences per 1,000 person-years; 95% CI, 75.43 to 156.20) versus 11.4% (51 of 446; 30.21 recurrences per 1,000 person-years; 95% CI, 22.96 to 39.74) in TERT mutation–positive versus –negative patients (HR, 3.46; 95% CI, 2.19 to 5.45). Recurrence rates were 68.6% (24 of 35; 211.76 recurrences per 1,000 person-years; 95% CI, 141.94 to 315.94) versus 8.7% (25 of 287; 21.60 recurrences per 1,000 person-years; 95% CI, 14.59 to 31.97) in patients harboring both mutations versus patients harboring neither mutation (HR, 8.51; 95% CI, 4.84 to 14.97), which remained significant after clinicopathologic cofactor adjustments. Disease-free patient survival curves displayed a moderate decline with BRAF V600E or TERT C228T alone but a sharp decline with two coexisting mutations.

Conclusion

Coexisting BRAF V600E and TERT C228T mutations form a novel genetic background that defines PTC with the worst clinicopathologic outcomes, providing unique prognostic and therapeutic implications.


Purpose

Concordance between parents of children with advanced cancer and health care providers has not been described. We aimed to describe parent-provider concordance regarding prognosis and goals of care, including differences by cancer type.

Patients and Methods

A total of 104 pediatric patients with recurrent or refractory cancer were enrolled at three large children’s hospitals. On enrollment, their parents and providers were invited to complete a survey assessing perceived prognosis and goals of care. Patients’ survival status was retrospectively abstracted from medical records. Concordance was assessed via discrepancies in perceived prognosis, statistics, and McNemar’s test. Distribution of categorical variables and survival rates across cancer type were compared with Fisher’s exact and log-rank tests, respectively.

Results

Data were available from 77 dyads (74% of enrolled). Parent-provider agreement regarding prognosis and goals of care was poor (, 0.12 to 0.30). Parents were more likely to report cure was likely (P < .001). The frequency of perceived likelihood of cure and the goal of cure varied by cancer type for both parents and providers (P < .001 to .004). Relatively optimistic responses were more common among parents and providers of patients with hematologic malignancies, although there were no differences in survival.

Conclusion

Parent-provider concordance regarding prognosis and goals in advanced pediatric cancer is generally poor. Perceptions of prognosis and goals of care vary by cancer type. Understanding these differences may inform parent-provider communication and decision making.



Purpose

The three-drug combination of lenalidomide, bortezomib, and dexamethasone (RVD) has shown significant efficacy in multiple myeloma (MM). The Intergroupe Francophone du Myélome (IFM) decided to evaluate RVD induction and consolidation therapies in a sequential intensive strategy for previously untreated transplantation-eligible patients with MM.

Patients and Methods

In this phase II study, 31 symptomatic patients age < 65 years were enrolled to receive three RVD induction cycles followed by cyclophosphamide harvest and transplantation. Patients subsequently received two RVD consolidation cycles and 1-year lenalidomide maintenance.

Results

Very good partial response rate or better at the completion of induction, transplantation, and consolidation therapy was 58%, 70%, and 87%, respectively. Maintenance upgraded responses in 27% of patients. Overall, 58% of patients achieved complete response, and 68% were minimal residual disease (MRD) negative by flow cytometry. The most common toxicities with RVD were neurologic and hematologic, including grade 1 to 2 sensory neuropathy (55%), grade 3 to 4 neutropenia (35%), and thrombocytopenia (13%). Two basal cell carcinomas in the same patient and one case of breast cancer were observed. There was no treatment-related mortality. With a median follow-up of 39 months, estimated 3-year progression-free and overall survival were 77% and 100%, respectively. None of the patients who achieved MRD negativity relapsed.

Conclusion

The transplantation program with RVD induction and consolidation followed by lenalidomide maintenance produced high-quality responses and showed favorable tolerability in patients with newly diagnosed MM. Overall, 68% of patients achieved MRD negativity; none of these patients relapsed. This program is being evaluated in the ongoing IFM/Dana-Farber Cancer Institute 2009 phase III study.



Purpose

The antibody–drug conjugate trastuzumab emtansine (T-DM1) combines the cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 (HER2) –targeted, antitumor properties of trastuzumab. T-DM1 has shown activity in phase I and II single-arm studies in patients with pretreated HER2-positive metastatic breast cancer (MBC) and has demonstrated superior efficacy and improved tolerability versus standard MBC treatments in randomized phase II and III studies. This analysis, combining available data from all single-agent T-DM1 studies to date, was conducted to better define the T-DM1 safety profile.

Patients and Methods

Six studies in patients with HER2-positive MBC who received T-DM1 3.6 mg/kg every 3 weeks and follow-up data from patients in an extension study were analyzed. Analyses included adverse events (AEs) by grade; AEs leading to death, drug discontinuation, or dose reduction; and select AEs.

Results

Among 884 T-DM1–exposed patients, the most commonly reported all-grade AEs were fatigue (46.4%), nausea (43.0%), thrombocytopenia (32.2%), headache (29.4%), and constipation (26.5%). The most common grade 3 to 4 AEs were the laboratory abnormalities of thrombocytopenia (11.9%) and increased AST serum concentration (4.3%). These were manageable and not generally associated with clinical symptoms. There were 12 AE-related deaths. AEs resulted in dose reductions in 17.2% of patients and drug discontinuations in 7.0%.

Conclusion

In this analysis of 884 T-DM1–exposed patients, grade 3 or greater AEs were infrequent and typically asymptomatic and manageable. This favorable safety profile makes T-DM1 treatment suitable for exploration in other breast cancer settings.


Purpose

To determine the developmental trajectory of early cognitive and adaptive skills in young children with retinoblastoma from diagnosis to 5 years of age.

Patients and Methods

Ninety-four patients with retinoblastoma treated according to an institutional protocol underwent serial assessments of cognitive and adaptive functioning at age 6 months and 1, 2, 3, and 5 years. Data were analyzed by treatment strata, with patients with 13q deletion analyzed separately.

Results

At baseline, across all patients (except those with 13q deletion), developmental functioning was comparable with the normative mean, with mean scores for all strata within the average range. However, at age 5 years, developmental functioning was in the low average range and significantly below normative means. The trajectories of developmental functioning demonstrated significant decline over time, although this varied by treatment group/strata. Patients treated with enucleation only evidenced the greatest decline in cognitive functioning; significant change was not observed in patients treated with other modalities. Notable declines in parent-reported communication skills were observed in the majority of patients. Patients with 13q deletion evidenced delayed cognitive functioning at baseline, but minimal declines were observed through age 3 years. However, significant decreases in adaptive functioning were demonstrated over time for the 13q deletion subset.

Conclusion

The declines in functioning observed in this study were unexpected, as was the poorer performance of the enucleation-only group. This highlights the necessity of continuing to assess cognitive functioning in patients with retinoblastoma as they age. Additional research is necessary to determine the long-term trajectory of cognitive development in this population.




Purpose

Patients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis.

Patients and Methods

We obtained prediagnostic sera from 20 cases with AL amyloidosis and 20 healthy controls matched for age, sex, race, and age of serum sample from the Department of Defense Serum Repository. Serum protein electrophoresis with immunofixation and serum free light chain (FLC) analysis were performed on all samples.

Results

An M-Ig was detected in 100% of cases and 0% of controls (P < .001). The M-Ig was present in 100%, 80%, and 42% of cases at less than 4 years, 4 to 11 years, and more than 11 years before diagnosis, respectively. The median FLC differential (FLC-diff) was higher in cases compared with controls at all time periods, less than 4 years (174.8 v 0.3 mg/L; P < .001), 4 to 11 years (65.1 v 2.2 mg/L; P < .001), and more than 11 years (4.5 v 0.4 mg/L; P = .03) before diagnosis. The FLC-diff was greater than 23 mg/L in 85% of cases and 0% of controls (P < .001). The FLC-diff level increased more than 10% per year in 84% of cases compared with 16% of controls (P < .001).

Conclusion

Increase of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years.



















Purpose

Conflicting reports remain regarding the association between vasectomy, a common form of male contraception in the United States, and prostate cancer risk. We examined prospectively this association with extended follow-up and an emphasis on advanced and lethal disease.

Patients and Methods

Among 49,405 US men in the Health Professionals Follow-Up Study, age 40 to 75 years at baseline in 1986, 6,023 patients with prostate cancer were diagnosed during the follow-up to 2010, including 811 lethal cases. In total, 12,321 men (25%) had vasectomies. We used Cox proportional hazards models to estimate the relative risk (RR) and 95% CIs of total, advanced, high-grade, and lethal disease, with adjustment for a variety of possible confounders.

Results

Vasectomy was associated with a small increased risk of prostate cancer overall (RR, 1.10; 95% CI, 1.04 to 1.17). Risk was elevated for high-grade (Gleason score 8 to 10; RR, 1.22; 95% CI, 1.03 to 1.45) and lethal disease (death or distant metastasis; RR, 1.19; 95% CI, 1.00 to 1.43). Among a subcohort of men receiving regular prostate-specific antigen screening, the association with lethal cancer was stronger (RR, 1.56; 95% CI, 1.03 to 2.36). Vasectomy was not associated with the risk of low-grade or localized disease. Additional analyses suggested that the associations were not driven by differences in sex hormone levels, sexually transmitted infections, or cancer treatment.

Conclusion

Our data support the hypothesis that vasectomy is associated with a modest increased incidence of lethal prostate cancer. The results do not appear to be due to detection bias, and confounding by infections or cancer treatment is unlikely.


Purpose

We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.

Patients and Methods

We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).

Results

We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).

Conclusion

In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.


Purpose

Corticosteroids are frequently used in cancer pain management despite limited evidence. This study compares the analgesic efficacy of corticosteroid therapy with placebo.

Patients and Methods

Adult patients with cancer receiving opioids with average pain intensity ≥ 4 (numeric rating scale [NRS], 0 to 10) in the last 24 hours were eligible. Patients were randomly assigned to methylprednisolone (MP) 16 mg twice daily or placebo (PL) for 7 days. Primary outcome was average pain intensity measured at day 7 (NRS, 0 to 10); secondary outcomes were analgesic consumption (oral morphine equivalents), fatigue and appetite loss (European Organisation for Research and Treatment of Cancer–Quality of Life Questionnaire C30, 0 to 100), and patient satisfaction (NRS, 0 to 10).

Results

A total of 592 patients were screened; 50 were randomly assigned, and 47 were analyzed. Baseline opioid level was 269.9 mg in the MP arm and 160.4 mg in the PL arm. At day-7 evaluation, there was no difference between the groups in pain intensity (MP, 3.60 v PL, 3.68; P = .88) or relative analgesic consumption (MP, 1.19 v PL, 1.20; P = .95). Clinically and statistically significant improvements were found in fatigue (–17 v 3 points; P .003), appetite loss (–24 v 2 points; P = .003), and patient satisfaction (5.4 v 2.0 points; P = .001) in favor of the MP compared with the PL group, respectively. There were no differences in adverse effects between the groups.

Conclusion

MP 32 mg daily did not provide additional analgesia in patients with cancer receiving opioids, but it improved fatigue, appetite loss, and patient satisfaction. Clinical benefit beyond a short-term effect must be examined in a future study.


Purpose

Cutaneous melanoma incidence is increasing. Most new cases are thin (≤ 1 mm) with favorable prognoses, but survival is nonetheless variable. Our aim was to investigate new prognostic factors and construct a nomogram for predicting survival in individual patients.

Patients and Methods

Data from 2,243 patients with thin melanoma were retrieved from prospectively maintained databases at six centers. Kaplan-Meier survival and crude cumulative incidences of recurrence were estimated, and competing risks were taken into account. Multivariable Cox regression was used to investigate survival predictors.

Results

Median follow-up was 124 months (interquartile range, 106 to 157 months); 12-year overall survival was 85.3% (95% CI, 83.4% to 87.2%). Median times to local, regional, and distant recurrence were 79, 78, and 107 months, respectively. Relapse was significantly related to age, Breslow thickness, mitotic rate (MR), ulceration, lymphovascular invasion (LVI), and regression; incidence was lower and subgroup differences were less marked for distant metastasis than for regional relapse. The worst prognosis categories were age older than 60 years, Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, presence of LVI, and regression ≥ 50%. Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, and LVI (all P = .001) were significantly associated with sentinel node positivity. Age, MR, ulceration, LVI, regression, and sentinel node status were independent predictors of survival and were used to construct a nomogram to predict 12-year overall survival. The nomogram was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.88).

Conclusion

Our findings suggest including LVI and regression as new prognostic factors in the melanoma staging system. The nomogram appears useful for risk stratification in clinical management and for recruiting patients to clinical trials.


Purpose

This study addressed whether age is prognostic for overall survival (OS) or progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC).

Patients and Methods

A total of 20,023 patients from 24 first-line clinical trials in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Primary age effects and interactions with age, sex, performance status (PS), and metastatic site were modeled using Cox proportional hazards stratified by treatment arm within study.

Results

Of total patients, 3,051 (15%) were age ≤ 50 years. Age was prognostic for both OS (P < .001) and PFS (P < .001), with U-shaped risk (ie, highest risk was evident in youngest and oldest patients). Relative to patients of middle age, the youngest patients experienced 19% (95% CI, 7% to 33%) increased risk of death and 22% (95% CI, 10% to 35%) increased risk of progression. The oldest patients experienced 42% (95% CI, 31% to 54%) increased risk of death and 15% (95% CI, 7% to 24%) increased risk of progression or death. This relationship was more pronounced in the first year of follow-up. Age remained marginally significant for OS (P = .08) when adjusted for PS, sex, and presence of liver, lung, or peritoneal metastases, and age was significant in an adjusted model for PFS (P = .005). The age effect did not differ by site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutational status.

Conclusion

Younger and older age are associated with poorer OS and PFS among treated patients with mCRC. Younger and older patients may represent higher-risk populations, and additional studies are warranted.


Purpose

To investigate the efficacy and safety of aerobic training (AT) in patients with cancer with medically stable heart failure (HF).

Patients and Methods

A retrospective analysis of 90 patients with cancer who have HF and who were randomly assigned to AT (n = 47) or guideline-based usual care (UC; n = 43) was performed. AT consisted of three supervised sessions per week at 20 to 45 minutes per session at 60% to 70% of heart rate reserve for 12 weeks followed by home-based sessions for 4 to 12 months. The primary end point was all-cause mortality and hospitalization. Secondary end points were other clinical events, safety, and change in exercise capacity (VO2peak) and health-related quality of life (HRQOL).

Results

Median follow-up was 35 months. In intention-to-treat (ITT) analyses, all-cause mortality or hospitalization at 2 years was 74% in the AT group compared with 67% in the UC group (adjusted hazard ratio [HR], 1.11; 95% CI, 0.69 to 1.77; P = .676). The incidence of cardiovascular mortality or cardiovascular hospitalization was significantly higher in the AT group compared with the UC group (41% v 67%; adjusted HR, 1.94; 95% CI, 1.12 to 3.16; P = .017). There were no differences in any VO2peak or HRQOL end points. In post hoc analyses based on adherence to AT, all-cause mortality and hospitalization was 66% in adherent patients (≥ 90 minutes per week) compared with 84% in nonadherent patients (< 90 minutes per week).

Conclusion

In ITT analyses, AT did not improve clinical outcomes in patients with cancer who had HF. Post hoc analyses suggested that patients not capable of adhering to the planned AT prescription may be at increased risk of clinical events.