S. Chopra

Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study.

PurposeThis trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone.Materials and methodsPatients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery.ResultsA total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03).ConclusionEscalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

Cisplatin Chemoradiotherapy vs Radiotherapy in FIGO Stage IIIB Squamous Cell Carcinoma of the Uterine Cervix: A Randomized Clinical Trial

Importance The evidence for concurrent chemoradiotherapy (CT-RT) in International Federation of Gynecology and Obstetrics (FIGO) stage IIIB squamous cell carcinoma of the uterine cervix is not robust. This study reports the final results of a randomized clinical trial of concurrent cisplatin-based CT-RT and radiotherapy alone (RT) in women with FIGO stage IIIB squamous cell carcinoma of the uterine cervix. Objective To investigate the benefit of concurrent CT-RT in FIGO stage IIIB squamous cell carcinoma of the uterine cervix. Design, Setting, and Participants This phase 3 open-label randomized clinical trial accrued 850 women in Mumbai, India, between July 7, 2003, and September 22, 2011. Of 2121 screened, 850 women with FIGO stage IIIB squamous cell carcinoma of the uterine cervix suitable for concurrent cisplatin chemotherapy were randomly assigned to CT-RT and RT using block randomization (1:1). The data were updated for a minimum follow-up period of 5 years until December 2016. The final analyses were performed in February and March 2017. This single-institution study was conducted at a tertiary cancer center setting. Interventions Randomization to receive RT (RT arm), comprising a combination of external beam RT (50 Gy in 25 fractions over 5 weeks) and brachytherapy, or to receive in addition to the same RT concurrent weekly cisplatin chemotherapy (40 mg/m2 per week) (CT-RT arm). Main Outcomes and Measures The primary end point was 5-year disease-free survival (DFS), defined as the time between the date of randomization and the date of any recurrence or death (whichever occurred first) in the intent-to-treat population. Results This trial included 424 women assigned to CT-RT (mean [SD] age, 49.4 [7.9] years) and 426 women assigned to RT (mean [SD] age, 49.3 [7.9] years). At a median follow-up of 88 months (interquartile range, 61.3-113.1 months), there were 222 recurrences and 213 deaths in the CT-RT arm and 252 recurrences and 243 deaths in the RT arm. The 5-year DFS was significantly higher in the CT-RT arm (52.3%; 95% CI, 52.2%-52.4%) compared with the RT arm (43.8%; 95% CI, 43.7%-43.9%), with a hazard ratio for relapse or death of 0.81 (95% CI, 0.68-0.98) (Pu2009=u2009.03). Similarly, the 5-year overall survival (OS) was significantly higher in the CT-RT arm (54.0%; 95% CI, 53.9%-54.1%) compared with the RT arm (46.0%; 95% CI, 45.9%-46.1%), with a hazard ratio for death of 0.82 (95% CI, 0.68-0.98; Pu2009=u2009.04). After adjusting for prognostic factors, CT-RT continued to be significantly superior to RT for DFS and OS. There was a higher incidence of acute hematological adverse effects in the CT-RT arm. Conclusions and Relevance Chemoradiotherapy using weekly cisplatin results in significantly better DFS and OS compared with RT in women with stage IIIB squamous cell carcinoma of the uterine cervix. This study provides level 1 evidence in the largest clinical trial reported so far in favor of concurrent weekly cisplatin chemotherapy in this setting. Trial Registration clinicaltrials.gov Identifier: NCT00193791

A Prospective Comparison of Computed Tomography with Transrectal Ultrasonography Assistance and Magnetic Resonance Imaging–Based Target-Volume Definition During Image Guided Adaptive Brachytherapy for Cervical Cancers

PURPOSEnAlthough magnetic resonance imaging (MRI) represents the gold standard for image guided adaptive brachytherapy (IGABT) for cervical cancer, the majority of brachytherapy (BT) continues to be guided by computed tomography (CT). However, CT seems to overestimate the target-volume definition, and the potential of transrectal ultrasonography (TRUS) needs further evaluation. This prospective, comparative study aimed to evaluate CT-based target contouring with the incorporation of TRUS during BT.nnnMETHODS AND MATERIALSnPatients with locally advanced cervical cancer undergoing magnetic resonance IGABT between January 2013 and March 2014 were included. During the BT procedure, TRUS imaging with central tandem in situ was acquired at 3 representative levels. Reference points/dimensions (D1-D4) of the hypoechoic region on TRUS images with respect to the central tandem were recorded. CT and magnetic resonance BT planning imaging was performed after BT application. The high-risk clinical target volume (HR-CTV) was contoured on CT scans with incorporation of clinical and TRUS imaging findings and was compared with the gold standard MRI-based target approach.nnnRESULTSnThe image sets of 25 patients (International Federation of Gynecology and Obstetrics clinical stage IIB [11; 44%] and IIIB [14; 56%]) were evaluable. The mean (±standard deviation) volumes of HR-CTV on CT and MRI imaging were 39.1 (±20) cm³ and 39 (±19) cm³, respectively (r = 0.92; P < .001). A significant correlation was found between the HR-CTV dimensions (width and thickness) of CT and MRI scans at various levels (r = 0.70-0.80; P < .001). In addition, the absolute differences in target dimensions between CT and MRI were <0.5 cm. A strong correlation was seen between CT and MRI for patients with medial and lateral parametrial invasion (P < .05) compared with no parametrial disease at BT. Furthermore, the mean differences in HR-CTV width between CT and MRI contours at various levels, irrespective of parametrial involvement, was only 0.1 to 0.4 cm.nnnCONCLUSIONSnThis study suggests that a CT-based target and organ-at-risk delineation using MRI at diagnosis and real-time TRUS information during BT seems comparable with the gold standard MRI-based approach in IGABT for cervical cancer.

Cancer Stem cells, CD44 and outcomes following chemoradiation in locally advanced cervical cancer: Results from a prospective study

PURPOSEnAlthough cancer stem cells (CSCs) have been reported across solid tumors, there is a dearth of data regarding CSC and its impact on outcomes of cervical cancer.nnnMETHODS AND MATERIALSnFrom October 2013 to December 2015, patients with squamous cancer of the cervix (stage IB2-IVA) were included. Pretreatment and posttreatment biopsy was obtained and immunohistochemistry was performed for SOX-2, OCT-4, Nanog, CD44, and Podoplanin. All patients received concurrent radiation and brachytherapy to an equivalent dose of 80 to 84xa0Gy to point A with concurrent weekly cisplatin. Correlation of CSC expression was performed with known prognostic factors. The effect of stem cell expression on disease outcomes was tested within multivariate analysis.nnnRESULTSnOne hundred fifty patients were included. The median dose to point A was 83xa0Gy (46-89xa0Gy) and a median of 4 cycles (range, 0-6 cycles) of chemotherapy was administered. At baseline, moderate to strong immunohistochemical expression of SOX-2, OCT-4, Nanog, CD44, and Podoplanin was observed in 12.8%, 4.8%, 24.4%, 15.5%, and 1.3% of patients, respectively. At median follow-up of 30xa0months (range, 3-51xa0months), locoregional and distant relapse was observed in 12.2% and 23.1% of patients, of whom 4.7% had both local and distant relapse. The 3-year disease-free survival rate was 87%. On multivariate analysis, moderate to high CSC expression and CD44 low status (hazard ratio [HR]xa0=xa08.8; 95% confidence interval [CI], 1.0-77.2; Pxa0<xa0.04) independently predicted for locoregional relapse-free survival. International Federation of Gynecology and Obstetrics stage (HRxa0=xa02.6; 95% CI, 1.3-5.4; Pxa0=xa0.004) and presence of residual tumor after external radiation (HRxa0=xa03.5; 95% CI, 1.8-6.5; Pxa0=xa0.0001) predicted for a detriment in disease-free survival.nnnCONCLUSIONSnThe presence of stem cell proteins and loss of CD44 independently predicts for reduced locoregional control in locally advanced cervical cancer. Further investigation into the interaction of stem cell and CD44 biology is warranted.