The Effect of Weight Change During Treatment With Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma

BackgroundThe relationship between weight change during treatment and survival remains poorly characterized in patients with metastatic renal cell carcinoma (mRCC).Patients and MethodsIn this retrospective analysis we included 3311 patients with mRCC treated in phase II/III first-line or second-line targeted therapy clinical trials and assessed the effect of weight change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) at 6 and 12 weeks from treatment initiation. Weight change was defined as weight loss (≥5% reduction), weight gain (≥2% increase), or stable weight from baseline. Survival analyses were performed using the Kaplan–Meier method and adjusted for known prognostic factors using Cox regression multivariable analysis.ResultsOverall, 1916 (58%) had stable weight, 936 (28%) had weight loss, and 459 (14%) had weight gain at 12 weeks. Patients with weight loss at 12 weeks had inferior OS compared with those with stable weight (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.322-1.688; P < .0001; median OS 18.7 vs. 26.9 months), and shorter PFS (HR, 1.315; 95% CI, 1.189-1.455; P < .0001; median PFS, 7.2 vs. 10.1 months). The ORRs for patients with weight loss, stable weight, and weight gain at 12 weeks were 23.4% (n = 219/936), 32.1% (n = 615/1916), and 35.9% (n = 165/459), respectively (adjusted odds ratio, 0.715; P = .03). Findings were consistent at 6 weeks. Adverse events were similar between groups.ConclusionWe showed that mRCC patients who experience weight loss during treatment have worse outcomes compared with patients with stable weight at 6 and 12 weeks of treatment. Weight loss at 6 weeks from treatment initiation might be an early clinical biomarker of worse survival and might provide prognostic utility.     

Impact on Health-Related Quality of Life of Induction Chemotherapy Compared With Concurrent Cisplatin and Radiation Therapy in Patients With Head and Neck Cancer

AimsOrgan preservation, an important goal in the treatment of head and neck squamous cell carcinoma (HNSCC), may include induction chemotherapy and cisplatin with radiation therapy (CRT). To our knowledge, no reports have directly compared the impact of induction chemotherapy with that of CRT on health-related quality of life (HRQOL).Materials and methodsIn a phase II trial, we assessed the HRQOL of patients treated with induction chemotherapy followed by CRT. Eligible patients had stage III–IV HNSCC. HRQOL questionnaires were administered at baseline, the end of induction (EOI), the end of CRT (EOCRT) and after CRT. Functional Assessment of Cancer Therapy (FACT version 4) assessed HRQOL. We carried out a comparison of changes in HRQOL from baseline to EOI and from EOI to EOCRT. This trial is registered with ClinicalTrials.gov (NCT01566435).ResultsThirty patients were enrolled in the study. Most HRQOL questionnaires were completed (88%). The mean total FACT scores did not differ from baseline to EOI (general: 83.8 versus 79.1, P = 0.08; head and neck: 109.7 versus 105.8, P = 0.33; Total Outcome Index: 69.7 versus 62.3, P = 0.03; respectively, using P ≤ 0.01 to adjust for multiple simultaneous tests of differences). However, total FACT scores significantly worsened from EOI to EOCRT (79.1 versus 62.3, P = 0.01; 105.8 versus 74.2, P < 0.01; 62.3 versus 34.2, P = 0.01; respectively). Within domains, the head and neck cancer subscale score did not differ from baseline to EOI (median 28.5 versus 27.0, P = 0.69), but significantly worsened from EOI to EOCRT (27.0 versus 9.5, P < 0.01). Swallowing, oral pain and voice quality improved from baseline to EOI, but worsened from EOI to EOCRT. Physical and functional scores worsened from baseline to EOI and from EOI to EOCRT. The emotional well-being score improved from baseline to EOI but worsened from EOI to EOCRT.ConclusionsOverall, HRQOL did not significantly change from baseline to EOI but dramatically worsened from EOI to EOCRT.     

Temozolomide as a Single Agent Maintenance Therapy in Elderly Patients With Primary CNS Lymphoma

IntroductionOptimal management of elderly patients with primary central nervous system lymphoma (PCNSL) after induction therapy is unclear. Whole-brain radiotherapy and autologous stem cell transplantation carry increased toxicity in patients older than 60 years of age, which might outweigh the benefits in this group. Temozolomide (TMZ) has established antineoplastic activity in the central nervous system in other disease states, with a favorable toxicity profile.Patients and MethodsWe report efficacy and tolerability in a series of 10 patients treated off-label with TMZ maintenance after completion of R-MPV (rituximab, methotrexate, procarbazine and vincristine) treatment for or primary diagnosed PCNSL.ResultsMedian progression-free survival (PFS) was 57 months, 2-year PFS was 67%, and 5-year PFS was 33%. Median overall survival (OS) was 63 months, 2-year OS was 88%, and 5-year OS was 57%. TMZ was generally well tolerated, with the most common toxicity of Grade 3 or higher being thrombocytopenia in 3 patients (30%).ConclusionThese outcomes suggest that TMZ might have activity for maintenance in elderly patients with PCNSL, when more aggressive treatments are contraindicated.     

Association of Hyponatremia With Survival in Patients With Castration-resistant Prostate Cancer: A Clinical Commentary

IntroductionThe aim of this study was to evaluate the prognostic value of hyponatremia in patients with castration-resistant prostate cancer (CRPC) undergoing docetaxel chemotherapy.Patients and MethodsWe retrospectively assessed 186 patients who received docetaxel chemotherapy in addition to androgen deprivation for CRPC between 2005 and 2015. We stratified the patients according to their pre-chemotherapy serum sodium level. Hyponatremia was defined as sodium < 135 mmol/L. A Cox proportional regression model was used to estimate overall survival (OS).ResultsThe median sodium level was 139 mmol/L (interquartile range, 137-141 mmol/L). Hyponatremia was detected in 13 (6.9%) patients. One-half of the patients died during the studied period. The presence of hyponatremia was associated with a decreased probability of OS (hazard ratio, 2.5; 95% confidence interval, 1.0-6.3; P = .04) in univariate analysis. These findings could not be confirmed in the multivariable OS model (P = .21).ConclusionWe observed an association between hyponatremia and worse survival outcomes in our patients with CRPC undergoing docetaxel chemotherapy. However, further well-designed studies with full workup of hyponatremia are needed to validate these findings and to identify the underlying causes for this association in patients with CRPC.     

Validation of the IMDC Prognostic Model in Patients With Metastatic Renal-Cell Carcinoma Treated With First-Line Axitinib: A Multicenter Retrospective Study

BackgroundThe objective of the study was to validate the characteristics of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model in patients treated with first-line axitinib in clinical practice.Patients and MethodsWe retrospectively evaluated 143 patients with metastatic renal-cell carcinoma who were treated with axitinib as the first-line therapy between October 2008 and February 2019. Overall survival (OS) was evaluated according to the IMDC prognostic model. We investigated the intragroup heterogeneity in the intermediate-risk group and divided these patients according to abnormal C-reactive protein (CRP) levels. An inverse probability of treatment-weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate the effects of the CRP-risk model of OS in the patients in the IMDC intermediate-risk group.ResultsA significant difference in OS was observed in patients in the IMDC intermediate- and poor-risk group, although no significant difference was observed between the IMDC favorable- and intermediate-risk group. Significantly shorter prognosis was observed in patients in the IMDC intermediate-risk group who had 2 risk factors and CRP ≥0.3 mg/dL (inter-high group) than in those with 1 risk factor or 2 risk factors with CRP <0.3 mg/dL (inter-low group). IPTW-adjusted Cox regression analysis revealed significant differences in the OS between the inter-low and inter-high groups.ConclusionThe IMDC prognostic model was active in patients who received first-line axitinib treatment. The combination of CRP value with the number of positive risk factors in the IMDC model might predict prognosis in patients with IMDC intermediate-risk treated with first-line axitinib.     

Outcomes in Organ Transplant Recipients With Prostate Cancer Treated With Radiotherapy

Background

Few data exist in the literature regarding outcomes of men with prostate cancer (CaP) who are receiving immunosuppression from prior organ transplantation. The aim of this study was to evaluate biochemical disease-free survival, distant metastasis–free survival, overall survival, and toxicity in patients with organ transplants who were later treated with definitive radiotherapy for CaP.

Synchronous Bilateral RCC Is Associated With Poor Recurrence-Free Survival Compared With Unilateral RCC: A Single-Center Study With Propensity Score Matching Analysis

BackgroundUnderstanding the tumorigenesis of bilateral cancers occurring in paired organs is essential for treatment planning and follow-up strategies. To the best of our knowledge, only a few studies compared the survival outcomes in patients with unilateral and bilateral renal cell carcinoma (RCC). We aimed to evaluate the survival outcomes of these patients after surgery and perform a further comparison of synchronous and metachronous bilateral RCCs.Materials and MethodsWe analyzed clinical data from a total of 2169 patients (98.0%) diagnosed with unilateral RCC and 44 patients (2.0%) diagnosed with bilateral RCC including 22 (50.0%) with synchronous (diagnosed concomitantly or within 3 months of the former tumor) and 22 (50.0%) with metachronous RCC at our institution. Comparative analysis of unilateral and bilateral RCC groups was conducted using propensity score matching analysis. Subgroup analysis of bilateral RCC including synchronous and metachronous RCCs was also performed.ResultsKaplan–Meier survival analysis showed a significantly decreased 5-year recurrence-free survival (RFS; 82.6% vs. 94.3%; log rank test, P = .045) in the bilateral RCC group compared with the unilateral group. In subgroup analysis, the metachronous RCC group showed significantly smaller mean pathologic tumor size (P = .011), and more favorable pathologic T stage (P = .036) compared with the synchronous RCC group. Kaplan–Meier survival analysis showed significantly decreased 5-year RFS in synchronous RCC compared with metachronous RCC (74.7% vs. 92.9%; log rank test, P = .028).ConclusionThe bilateral RCC group showed significantly decreased 5-year RFS compared with the unilateral RCC group. Importantly, the synchronous RCC group manifested more adverse features than the metachronous group.     

Population-based cancer registration in Indonesia

Cancer is a major public health problem in Indonesia, becoming the 7th largest cause of death based on a national survey in 2007, accounting for 5.7 of all mortality. A cancer registry was started in 1970, but it was partial and was stopped mainly because no government body was responsible. Realizing the above situation, the Indonesian government established the Sub Directorate of Cancer Control within the Ministry of Health, with responsibility for developing a national cancer control program, including a cancer registry. A sustainable cancer registry was then started in 2007 within Jakarta Province, first hospital-based but then expanded to be population-based. Steps of cancer registration in Jakarta are data collection, data verification, data validation, data management and analysis, and data publication. Data collection is conducted by health facilities (hospitals, laboratories, primary health centers) at the district/municipal level, with reports to the provincial level. Data are collected passively by holding meetings every three months in the district/municipality. Verification of data is the responsibility of the medical doctor or pathologist in each data source. Data validation is conducted by a team in the cancer registry, consisting of district/municipal/province health officers, pathologists, and registrars. Data management and analyses are conducted by a cancer registry team at the provincial level, assisted by the national team. We use software named Indonesian Cancer Registry System (SRIKANDI) which is adopted from CanReg4 IARC. Data from the population-based cancer registry in Jakarta Province showed the leading cancers among females in 2005-2007 to be breast cancer, cervical cancer, ovarian cancer, colorectal cancer and among males are bronchus and lung cancer, colorectal cancer, liver cancer, pharyngeal cancer, and prostate cancer. The leading childhood cancers are leukaemia and retinoblastoma.     

A Predictor of Early Disease Recurrence in Patients With Breast Cancer Using a Cell-free RNA and Protein Liquid Biopsy

IntroductionCirculating biomarkers have been increasingly used in the clinical management of breast cancer. The present study evaluated whether RNAs and a protein present in the plasma of patients with breast cancer might have utility as prognostic biomarkers complementary to existing clinical tests.Patients and MethodsWe performed microarray profiling of small noncoding RNAs in plasma samples from 30 patients with breast cancer and 10 control individuals. Two small noncoding RNAs, including microRNA (miR)-923, were selected and quantified in plasma samples from an evaluation cohort of 253 patients with breast cancer, using droplet digital polymerase chain reaction. We also measured cancer antigen (CA) 15-3 protein levels in these samples. Cox regression survival analysis was used to determine which markers were associated with patient prognosis.ResultsAs independent markers of prognosis, the plasma levels of miR-923 and CA 15-3 at the time of surgery for breast cancer were significantly associated with prognosis, irrespective of treatment (Cox proportional hazards, P = 3.9 × 10⁻³ and 1.9 × 10⁻⁹, respectively). After building a multivariable model with standard clinical and pathological features, the addition of miR-923 and CA 15-3 information into the model resulted in a significantly better predictor of disease recurrence in patients, irrespective of treatment, compared with the use of clinicopathological data alone (area under the curve at 3 years, 0.858 vs. 0.770 with clinicopathological markers only; P = .017).ConclusionWe propose that the plasma levels of miR-923 and CA 15-3, combined with standard clinicopathological predictors, could be used as a preoperative, noninvasive estimate of patient prognosis to identify which women might need more aggressive treatment or closer surveillance after surgery for breast cancer.