Timur Mitin

Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial

BACKGROUND We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer. METHODS In our randomised phase 2 trial, we enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA. We randomly allocated patients to receive paclitaxel plus cisplatin (paclitaxel group) or fluorouracil plus cisplatin (fluorouracil group) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage (T2 vs T3-4). Patients and physicians were aware of treatment assignment. All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40·3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64·3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemoradiotherapy. If, after induction, persistent disease was graded as T1 or worse, we recommended patients undergo cystectomy and adjuvant chemotherapy. We assessed the primary endpoints of rates of treatment completion and toxic effects in all randomly allocated patients. This study is registered with ClinicalTrials.gov, number NCT00055601. FINDINGS Between Dec 13, 2002, and Jan 11, 2008, we enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5·0 years (IQR 5·0-6·2). Of 46 patients in the paclitaxel group, 45 (98%) completed induction (16 [35%] with grade 3-4 toxicity), 39 (85%) completed induction and consolidation (11 [24%] with grade 3-4 toxicity due to consolidation), and 31 (67%) completed the entire protocol with adjuvant chemotherapy. 34 (85%) of 40 assessable patients in the paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy. Of 47 patients in the fluorouracil group, 45 (96%) completed induction (nine [19%] with grade 3-4 toxicity), 39 (83%) completed induction and consolidation (12 [26%] had grade 3-4 toxicity due to consolidation), and 25 (53%) completed the entire protocol with adjuvant chemotherapy. 31 (76%) of 41 assessable patients in the fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy. Five (11%) patients treated with the paclitaxel regimen and three (6%) patients treated with the fluorouracil regimen developed late grade 3-4 radiotherapy toxicities. 11 (24%) patients treated with the paclitaxel regimen and 16 (34%) patients treated with the fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy. One patient (in the fluorouracil group) died during follow-up. Six (13%) patients in the paclitaxel group and in three (6%) patients in the fluorouracil group discontinued due to treatment-related toxicity. INTERPRETATION In the absence of phase 3 data, our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer. FUNDING US National Cancer Institute.

Changes in treatment patterns for patients with locally advanced rectal cancer in the United States over the past decade: An analysis from the National Cancer Data Base

In the United States, neoadjuvant chemoradiotherapy (NACRT) is widely accepted as the standard of care in the treatment of patients with locally advanced rectal cancer. In the current study, the authors attempted to examine patterns of treatment in the United States over the past decade.

Weight Gain on Androgen Deprivation Therapy: Which Patients Are at Highest Risk?

OBJECTIVE To identify factors associated with weight gain at 1 year from initiation of androgen deprivation therapy (ADT). METHODS A retrospective review assessed weight change among 118 men with nonmetastatic prostate cancer treated with ADT for at least 6 months. Outcome associations were tested using 2-tailed t tests and linear regression. RESULTS Men in our cohort had significant weight gain (+1.32 kg, P=.0005) in the 1 year after ADT initiation. Three risk factors for weight gain on ADT were identified as follows: age<65 years (2.72 kg gained, P=.001), body mass index (BMI)<30 (1.98 kg gained, P=.00002), and nondiabetic status (1.56 kg gained, P=.0003). Multivariable regression found both age<65 years (beta=4.01, P=.02) and BMI<30 (beta=3.57, P=.03) to be independently predictive of weight gain, whereas nondiabetic status was nonsignificantly predictive of weight gain (beta=2.14, P=.29). Weight change was further stratified by the total number of risk factors present (risk score): scores of 0, 1, 2, and 3 risk factors corresponded to weight changes of -1.10, +0.41, +1.34, and +3.79 kg, respectively (P-trend=.0005). CONCLUSION Age<65 years and BMI<30 were both independently associated with weight gain 1 year after starting ADT. Increasing weight gain was also strongly associated with increasing number of baseline risk factors present. Despite traditional concerns about ADT in unhealthy men, these data suggest younger, healthier patients may be at higher risk for gaining weight on ADT and should be counseled accordingly.

Long-term outcomes among patients who achieve complete or near-complete responses after the induction phase of bladder-preserving combined-modality therapy for muscle-invasive bladder cancer: A pooled analysis of NRG Oncology/RTOG 9906 and 0233

PURPOSE To investigate the differences in outcomes among patients with muscle-invasive bladder cancer on NRG Oncology Radiation Therapy Oncology Group protocols 9906 and 0233 who achieved complete response and near-complete response after induction chemoradiation and then completed bladder-preserving therapy with chemoradiation therapy (chemo-RT) to full dose (60-64 Gy). PATIENTS AND METHODS A pooled analysis was performed on 119 eligible patients with muscle-invasive bladder cancer enrolled on NRG Oncology Radiation Therapy Oncology Group trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose of at least 60 Gy. Bladder recurrence, salvage cystectomy rates, and disease-specific survival were estimated by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. RESULTS Among the 119 eligible patients, 101 (85%) achieved T0, and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36 of 101 T0 patients (36%) versus 5 of 18 Ta or Tis patients (28%) experienced bladder recurrence (P=.52). Thirteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, compared with 1 patient among near-complete responders (P=.63). Disease-specific, bladder-intact, and overall survivals were not significantly different between T0 and Ta/Tis cases. CONCLUSIONS The bladder recurrence and salvage cystectomy rates of the complete and the near-complete responders were similar. Therefore it is reasonable to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy with consolidation chemo-RT to full dose (60-64 Gy).

Urological cancer. The benefits of intermittent androgen-deprivation therapy.

The large randomized study by Crook et al. demonstrated that intermittent administration of androgen deprivation therapy should be considered the standard of care when patients with moderate and well-differentiated localized prostate cancer are treated for rising PSA levels after definitive radiotherapy.

The Red Beam: Past, Present, and Future of Radiation Oncology in Russia

The history of medicine and science in Russia is full of global “firsts,” and Russians are rightly proud of this scientific heritage. Even non-Russians with a working knowledge of scientific history can cite, for instance, that the periodic table of elements was conceived by Dmitri Mendeleev, the first virus was isolated by Dmitry Ivanovski, and the first extraterrestrial satellite placed in orbit and first manned space flight, respectively, were accomplished by teams of Soviet scientists and engineers. However, despite this auspicious history, scientific progress in Tsarist Russia and the Soviet Union was not immune to the historical convulsions of the 20th century. Consequently, rather than a steady march of progress, the history of Russian science can better be described as a cycle that alternated between periods of great discovery and intervals of repression and backsliding. The specific disciplines of radiation biology and nuclear medicine were not exempt from the ebb and flow of this historical pattern. Within the Russian scientific tradition, radiation and its application in oncology have deep roots. Therapeutic radiation therapy in Russia dates back to 1903, when a

Preoperative carboplatin and paclitaxel-based chemoradiotherapy for esophageal carcinoma: results of a modified CROSS regimen utilizing radiation doses greater than 41.4 Gy

Trimodality therapy for resectable esophageal and gastroesophageal junction cancers utilizing preoperative radiotherapy with concurrent carboplatin and paclitaxel-based chemotherapy is being increasingly utilized secondary to the results of the phase III CROSS trial. However, there is a paucity of reports of this regimen as a component of chemoradiotherapy in North America. We aim to report on our clinical experience using a modified CROSS regimen with higher radiotherapy doses. Patients with advanced (cT2-cT4 or node positive) esophageal or gastroesophageal junction carcinoma who received preoperative carboplatin/paclitaxel-based chemoradiotherapy with radiation doses of greater than 41.4 Gray (Gy) followed by esophagectomy were identified from an institutional database. Patient, imaging, treatment, and tumor response characteristics were analyzed. Twenty-four patients were analyzed. All but one tumor had adenocarcinoma histology. The median radiation dose was 50.4 Gy. Pathologic complete response was achieved in 29% of patients, with all receiving 50.4 Gy. Three early postoperative deaths were seen, due in part to acute respiratory distress syndrome and all three patients received 50-50.4 Gy. With a median follow-up of 9.4 months (23 days-2 years), median survival was 24 months. Trimodality therapy utilizing concurrent carboplatin/paclitaxel with North American radiotherapy doses appeared to have similar pathologic complete response rates compared with the CROSS trial, but may be associated with higher toxicity. Although the sample size is small and further follow-up is necessary, radiation doses greater than 41.4 Gy may not be warranted secondary to a potentially increased risk of severe radiation-induced acute lung injury.

HIV positivity and anal cancer outcomes: A single-center experience

BACKGROUND Anal cancer remains common among human immunodeficiency virus (HIV) patients. Chemoradiation has had mixed results. We evaluated outcome differences by HIV status. METHODS We retrospectively analyzed 14 HIV+ and 72 HIV- anal cancer patients (2000 to 2013). Outcomes included chemoradiation tolerance, recurrence, and survival. RESULTS HIV+ patients were more often male (100% vs 38%, P < .001) but diagnosed at similar stages (P = .49). They were less likely to receive traditional chemotherapy (36% vs 86%, P < .001). Recurrence (P = .55) and survival time (P = .48) were similar across groups. HIV+ patients had similar colostomy-free survival (P = .053). Receipt of 5-fluorouracil/mitomycin C (MMC) chemotherapy predicted recurrence-free and overall survival (Hazard ratios .278, .32). HIV status did not worsen recurrence (P = .71) or survival (P = .57). CONCLUSIONS HIV+ patients received more non-MMC-based chemoradiation but had equivalent colostomy-free, recurrence, and overall survival. Use of 5-fluorouracil/MMC chemotherapy increased after 2008.

The Use of Hypofractionated Whole Breast Irradiation in Treatment of Patients With Early-Stage Breast Cancer in the United States

RESULTS Hypofractionated WBI increased from 10.6% (95% CI, 8.8%-12.5%) in 2008 to 34.5% (95% CI, 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95% CI, 6.0%-10.2%) in 2008 to 21.2% (95% CI, 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1 year after diagnosis were

Limited Use of Adjuvant Therapy in Patients With Resected Gallbladder Cancer Despite a Strong Association With Survival

28 747 for hypofractionated and