Low-Dose-Rate versus High-Dose-Rate intracavitary brachytherapy in cervical cancer - Final Results of a Phase III randomized trial.

PURPOSE: Intracavitary brachytherapy using High-Dose-Rate (HDR) and Low-dose-rate (LDR) in cervical cancer has been utilized. We report the long-term final results of a large randomized trial in terms of toxicities and efficacy. METHODS AND MATERIALS: Between 1996 to 2005, 816 patients were randomized to LDR (n = 441 patients) or HDR brachytherapy (n = 369 patients) stratified by FIGO Stage grouping. Patients with Stage I-II received external irradiation of 40 Gy in 20 fractions (with midline block (MLB)) followed by either 2 LDR Intracavitary applications of 30 Gy to point A (2-3 weeks apart) or 5 HDR Intracavitary applications of 7 Gy to point A once weekly. Patients with Stage III received 50 Gy in 25 fractions (with MLB after 40 Gy) followed by either one application of LDR 30 Gy to point A or three applications of HDR 7 Gy to point A once weekly. RESULTS: With a median follow-up was 64 months (interquartile range [IQR]: 21 - 111), moderate to severe rectal and bladder complications were higher in LDR arm as compared to HDR arm (9.7% vs. 3.6%; p = 0.02) and (10.5% vs. 5.5%; p = 0.06) for Stage I-II. No difference in rectal or bladder complications for Stage III patients. Disease free and overall survivals were similar in both the arms for all stages. CONCLUSIONS: HDR intracavitary brachytherapy with 7 Gy per fraction weekly is superior to LDR in terms of late rectal and bladder complications. Local control rates and survivals are similar irrespective of stages.

Dose escalated concurrent chemo-radiation in borderline resectable and locally advanced pancreatic cancers with tomotherapy based intensity modulated radiotherapy: a phase II study.

BACKGROUND: We report the response and outcomes of borderline resectable and locally advanced pancreatic cancer (BRPC & LAPC) patients treated with dose escalated neoadjuvant intensity modulated radiotherapy (IMRT). METHODS: Thirty newly diagnosed patients with BRPC (n=18) and LAPC (n=12) (NCCN criteria V 2.2.12) were accrued in this prospective study from 2008-2011. All patients received neoadjuvant chemoradiation (NACRT) using Helical Tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor volume (GTV) and 45 Gy over 25 fractions to suspected microscopic extension) along with weekly gemcitabine. RESULTS: Fifteen patients (50%) had a partial response. A complete metabolic response (CMR) on PET was seen in 9 patients (30%). Among BRPC, 9 patients (50%) were surgically explored and 7 underwent R0 resection (39%). The median follow up of surviving patients was 85 [interquartile range (IQR): 64.5-85.8] months. The median progression free survival (PFS) was 13 months for BRPC and 8.8 months for LAPC. The median overall survival (OS) was 17.3 months for BRPC and 11.8 months for LAPC. Among patients undergoing R0 resection, the median PFS and OS was 27 and 35.5 months respectively. CONCLUSIONS: Dose escalated radiotherapy with concurrent chemotherapy is feasible and can downsize some tumors resulting in surgery in about 39% of the BRPC.

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.

PURPOSE: Although 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. METHODS AND MATERIALS: Patients 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. RESULTS: The 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. CONCLUSIONS: This 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.

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) (P = .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; P = .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 comparative analysis of quality of life after postoperative intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for cervical cancer.

AIMS: The aim of this study is to compare the quality of life (QOL) between adjuvant three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) for cervical cancer. MATERIALS AND METHODS: QOL assessment was done at the baseline and then longitudinally after completing (chemo) radiation. All patients completed EORTC QLQ-C30 and EORTC QLQ Cx-24 modules. Independent-sample t-test was used to compare the mean scores between the two groups. Analysis of variance was used to compare differences in QOL measures over the six time points (baseline, post-RT, 3, 6, 9, and 12 months after treatment) and between treatment groups (3DCRT vs. IMRT). Linear mixed model was also performed to account for attrition. RESULTS: Overall, 64 patients (image-guided IMRT, n = 40 and 3DCRT, n = 24) completed QOL assessment. The median age and follow-up period were 48 years and 15.5 months, respectively. General QOL domains such as emotional (at 12 months, P = 0.04) and social (at 3 months, P = 0.02 and 12 months, P = 0.03) were better with IMRT. Pain (12 months, P = 0.03); fatigue (12 months, P = 0.05); nausea and vomiting (12 months, P = 0.03); insomnia (post-RT, P = 0.05 and 12 months, P = 0.03); appetite loss (post-RT and 12 months, P = 0.04); and diarrhea (6 months, P = 0.02 and 12 months, P = 0.003) scores were significantly better with IMRT. On linear mixed model analysis, there was a significant interaction between treatment cohort and assessment intervals for physical, emotional, and social functioning, appetite loss, diarrhea, lymphedema, and menopausal symptom scores were significantly better with IMRT. CONCLUSIONS: Treatment technique (IMRT vs. 3DCRT) impacts early QOL in undergoing adjuvant radiation for cervical cancer.

Optimal bladder filling during high-dose-rate intracavitary brachytherapy for cervical cancer: a dosimetric study.

PURPOSE: The aim of this study is to compare 3D dose volume histogram (DVH) parameters of bladder and other organs at risk with different bladder filling protocol during high-dose-rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer, and to find optimized bladder volume. MATERIAL AND METHODS: This dosimetric study was completed with 21 patients who underwent HDR-ICBT with computed tomography/magnetic resonance compatible applicator as a routine treatment. Computed tomography planning was done for each patient with bladder emptied (series 1), after 50 ml (series 2), and 100 ml (series 3) bladder filling with a saline infusion through the bladder catheter. Contouring was done on the Eclipse Planning System. 7 Gy to point A was prescribed with the standard loading patterns. Various 3D DVH parameters including 0.1 cc, 1 cc, 2 cc doses and mean doses to the OAR's were noted. Paired t-test was performed. RESULTS: The mean (± SD) bladder volume was 64.5 (± 25) cc, 116.2 (± 28) cc, and 172.9 (± 29) cc, for series 1, 2, and 3, respectively. The 0.1 cm3,1 cm3, 2 cm3 mean bladder doses for series 1, series 2, and series 3 were 9.28 ± 2.27 Gy, 7.38 ± 1.72 Gy, 6.58 ± 1.58 Gy; 9.39 ± 2.28 Gy, 7.85 ± 1.85 Gy, 7.05 ± 1.59 Gy, and 10.09 ± 2.46 Gy, 8.33 ± 1.75 Gy, 7.6 ± 1.55 Gy, respectively. However, there was a trend towards higher bladder doses in series 3. Similarly, for small bowel dose 0.1 cm3, 1 cm3, and 2 cm3 in series 1, 2, and 3 were 5.44 ± 2.2 Gy, 4.41 ± 1.84 Gy, 4 ± 1.69 Gy; 4.57 ± 2.89 Gy, 3.78 ± 2.21 Gy, 3.35 ± 2.02 Gy, and 4.09 ± 2.38 Gy, 3.26 ± 1.8 Gy, 3.05 ± 1.58 Gy. Significant increase in small bowel dose in empty bladder (series 1) compared to full bladder (series 3) (p = 0.03) was noted. However, the rectal and sigmoid doses were not significantly affected with either series. CONCLUSIONS: Bladder filling protocol with 50 ml and 100 ml was well tolerated and achieved a reasonably reproducible bladder volume during cervical brachytherapy. In our analysis so far, there is no significant impact of bladder filling on DVH parameters, although larger bladders tend to have higher doses. Small bowel doses are lesser with higher bladder volumes. Further evaluation and validation are necessary.

Transabdominal Ultrasonography-Defined Optimal and Definitive Bladder-Filling Protocol With Time Trends During Pelvic Radiation for Cervical Cancer.

PURPOSE: Advanced radiotherapy techniques have emphasized on the importance of accurate target volume localization and delineation. The aim of this study was to determine time taken to achieve moderate bladder volume under physiological conditions, using transabdominal ultrasound. MATERIALS AND METHODS: Patients with cervical cancer undergoing radical radiation with or without concomitant chemotherapy underwent serial ultrasound to estimate bladder filling. With a strict bladder protocol of consuming 1000 mL of water orally over 30 minutes after emptying the bladder, ultrasound was done after 45 minutes from bladder emptying time and repeated at 15-minute interval till 300 (25) mL filling was achieved and repeated every week. RESULTS: Forty-six patients with weekly ultrasound for bladder-filling documentation were evaluated. The mean (standard deviation) bladder volume measured at 45 minutes was 220 (93), 210 (95), 195 (91), 195 (96), and 190 (85) mL (average: 200; median: 195 mL) for the first to fifth week, respectively, and the mean (standard deviation) volume at 75 minutes was 300 (95), 310 (80), 290 (80), 295 (80), and 285 (70) mL (average: 295; median: 300 mL). The mean (standard deviation) time for bladder filling to 300 mL in the first, second, third, fourth, and fifth week was 57 ( 13.5), 67 (16.6), 66 (16.7), 66 (15.5), and 69 (17.1) minutes, respectively. CONCLUSION: Bladder filling to a definitive moderate volume at a reasonably fixed time period in each week of radiation is well tolerated, feasible, and measurable by weekly transabdominal ultrasound measurements.

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study.

PURPOSE: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. METHODS AND MATERIALS: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/ß of 10 [EQD2]10 = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). RESULTS: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. CONCLUSIONS: Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.

Clinical impact of prostate specific antigen (PSA) inter-assay variability on management of prostate cancer.

PURPOSE: To evaluate the inter-assay variability of six commercially available prostate specific antigen (PSA) assays, its clinical impact in prostate cancer (PCa) and comparison of automated versus manual assays. PATIENTS AND METHODS: Sera from 495 patients (425 with PCa and 70 men with Benign Prostatic Hyperplasia (BPH), were measured with six different assays [three automated assays (a-PSA) and three manual ELISA based assay (m-PSA)]. Variability, agreement and bias were measured and compared among assays using Bland Altman plots and Passing and Bablok regression analysis. The possible impact of inter-assay variability on important clinical scenarios was also studied. RESULTS: All the assays were well correlated (r: 0.88-0.98); however there was significant disagreement and bias between the systems, which were more pronounced among the a-PSA assays. The Bland Altman plot showed that the variability was high between the m-PSA assays and the standard Abbott system with mean difference of 3.8-5.8ng/ml. In contrast, the a-PSA had better agreement with mean difference of 0.8-2.3ng/ml. Beckman Coulter showed the best agreement to the institutional reference (slope-1.097; 95% CI: 1.06-1.14; p<0.05, and intercept-0.20; 95% CI-0.38-0.58; p<0.05, Passing Bablok). It led to significant variability in PCa risk stratification and failure to detect biochemical failure in more than 50% cases. CONCLUSIONS: The discrepancies between the assays lead to significant clinical misinterpretation with risk group migration and detection of biochemical failure post radiotherapy. There are significant discordances between automated and ELISA based assays.

Brachytherapy in India - a long road ahead.

Brachytherapy can play a very important role in the definitive cure by radiation therapy in India. However, except for in a handful of centres, the majority of hospitals use it only for intracavitary treatment. The most probable reasons for such are the lack of logistical resources in terms of trained personal and supporting staff, rather than lack of radiotherapy machines and equipment. In this article, the authors look into the various aspects of brachytherapy in India: from its beginning to present days. The authors point out the resources available, shortcomings, and some possible solutions to make use of brachytherapy more popular and effective. Apart from presenting a picture of the present scenario, the article pays attention to the positive signs of brachytherapy becoming more popular in the near future.

Reirradiation using high-dose-rate brachytherapy in recurrent carcinoma of uterine cervix.

PURPOSE: To assess the feasibility of reirradiation with image-based high-dose-rate brachytherapy in previously irradiated patients with recurrent carcinoma of uterine cervix. METHODS AND MATERIALS: Thirty previously irradiated patients diagnosed with central recurrence were treated with reirradiation. Martinez Universal Perineal Implant Template was used in 24 patients and Vienna applicator in 6 patients. Median interval between two radiation schedules was 25 months. Median delivered dose was 42 Gy equivalent dose at 2 Gy (EQD2; interquartile range, 37-46 Gy EQD2). RESULTS: All 30 patients tolerated reirradiation well. Complete response was seen in 23 (76%) patients. With a median followup of 25 months, 2-year local control, disease-free survival, and overall survival were 44%, 42%, and 52%, respectively. Fifteen patients developed local recurrences; Local control rate was significantly higher with doses >40 Gy EQD2 (52% vs. 34%; p = 0.05). Disease-free survival was better for patients with longer interval (>25 months) between two radiotherapy schedules. Grade III radiation proctitis and cystitis was seen in 3 patients each, and Grade II small bowel toxicity was seen in 3 patients. CONCLUSIONS: Reirradiation using high-dose-rate brachytherapy is feasible with acceptable outcomes in isolated local recurrence deemed unsuitable for surgery. The outcome is better with higher doses.

Template-based high-dose-rate interstitial brachytherapy in gynecologic cancers: a single institutional experience.

PURPOSE: To report the outcome and toxicities of radical external beam radiotherapy (EBRT) and template-based high-dose-rate interstitial brachytherapy (ISBT) in patients diagnosed with cervical cancer undergoing inadvertent surgery, vault cancers, and vaginal cancers at our institution. METHODS AND MATERIALS: Between January 2000 and December 2008, 113 patients (37 patients of cervical cancer post-inadvertent surgery, 57 patients with vault cancers, and 19 patients with primary vaginal cancers) were treated with Martinez Universal Perineal Interstitial Template brachytherapy boost after EBRT. The median EBRT dose was 50 Gy, median ISBT dose was 20 Gy, whereas median total dose was 73 Gy equivalent dose at 2 Gy per fraction in all three groups. RESULTS: Median followup of surviving patients for the whole group was 43 months (interquartile range, 19-67 months). The 3-year actuarial disease-free survival and overall survival for three groups was 61%, 61%, 59% and 64%, 64%, and 56%, respectively. Grade III/IV rectal toxicity was seen in 11 (10%) patients, bladder toxicity in 5 (4.5%) patients, whereas 7 (6%) patients developed Grade III small bowel toxicity. Residual disease at brachytherapy had significant impact on DFS and OS. Other factors such as age, disease volume, parametrial extension, and vaginal extension did not impact the survivals. CONCLUSIONS: Martinez Universal Perineal Interstitial Template-based high-dose-rate ISBT boost in gynecologic cancer results in a reasonable outcome in terms of survivals with acceptable late toxicities. The use of template-based ISBT is associated with a definite learning curve.

Helical tomotherapy-based hypofractionated radiotherapy for prostate cancer: a report on the procedure, dosimetry and preliminary clinical outcome.

CONTEXT: Hypofractionated intensity-modulated radiotherapy (IMRT) under image guidance using helical tomotherapy for prostate cancer improves therapeutic ratio. AIMS: To report on clinical and dosimetric experience using hypofractionated helical tomotherapy for prostate cancer. SETTINGS AND DESIGN: Prospective consecutive case series as feasibility study approved by Institutional Review Board (IRB) (2007-11). MATERIALS AND METHODS: The staging work-up, risk stratification, simulation, contouring, planning, online matching and treatment delivery methodology are described in detail. The doses to (prostate and nodal) PTV and organs at risk (bladder, rectum, bowel and femoral heads) are described. The audit of online matching was used to determine set-up errors, PTV margins and resultant translational vector. We also report the outcomes in terms of biochemical relapse-free survival and acute toxicity. RESULTS: Fifty-three consecutive patients were included. The baseline PSA was 23 ng/ml (1.60-100.37). The prostate BED3 ranged from 110-129 Gy (α/ß for prostate 1.5-3 Gy) and nodal 72-87.68 Gy. The required PTV margin by van Hark's formula for lateral, longitudinal and vertical axes were 11.30, 9.95 and 13.49 mm, respectively with resultant vectors 3-15 mm. There was 7% to 8% chance of missing part of CTV in absence of image guidance. There was only one patient requiring premature conclusion at 45 Gy due grade 3 genitourinary toxicity. At median follow-up of 23 months, biochemical relapse-free survival rate is 95.2%. CONCLUSIONS: Hypofractionated IMRT under image guidance using helical tomotherapy for prostate cancer is feasible with acceptable acute toxicity and may be advantageous in high throughput centers.

Treatment and outcome in cancer cervix patients treated between 1979 and 1994: a single institutional experience.

INTRODUCTION: A retrospective review in patients with carcinoma cervix to evaluate the changes and trends in demographics, evolution of protocols, and outcome analysis over 16 years. MATERIALS AND METHODS: This is a retrospective study of 6234 patients with carcinoma of the cervix treated with radical intent between 1979 and 1994. All the work-up, staging investigations, treatment details, radiation protocols, outcomes, and toxicities were noted, compiled, and analyzed. RESULTS: With a mean age of 46 years (range: 18-90 years; median: 45 years), 669 (11%) patients were in stage Ib, 284 (5%) were in stage IIa, 1891 (30%) were in stage IIb, 69 (1%) were in stage IIIa, and 3321 (53%) were in stage IIIb. With a median follow-up of 68 months (57-79 months) for the entire group, there was no significant difference in the outcome of 953 patients with international federation of gynecology and obstetrics (FIGO) Ib-IIa treated after radical surgery, pre-operative radiation therapy (pre-op RT) + Sx or after radical radiation; their disease-free survival (DFS) was 60-62% at 8 years. In our series of 1891 patients with stage IIb and 3321 with stage IIIb, a respective DFS of 56% and 40% was achieved at 8 years. CONCLUSION: Over the last two decades, with the acquisition of newer facilities and inception of Joint Clinics, there has been a significant refinement in the treatment protocols and outcome. Improving radiation strategies to improve therapeutic ratio is the key to success.

Comparison of 2 contouring methods of bone marrow on CT and correlation with hematological toxicities in non-bone marrow-sparing pelvic intensity-modulated radiotherapy with concurrent cisplatin for cervical cancer.

OBJECTIVES: To compare volumes and dose volume histogram (DVH) parameters for bone marrow contours using 2 methods on computed tomography (CT) and correlation with grade 2 or higher hematological toxicity (HT) in patients with cervical cancer treated with non-bone marrow-sparing intensity-modulated radiotherapy (IMRT) with concurrent cisplatin. MATERIALS AND METHODS: The planning CT scans of 47 patients prospectively enrolled and treated with IMRT arm of a phase 2 trial (NCT00193804) contoured for pelvic bone marrow in 2 sets; whole bone (WB), and freehand (FH) inner cavity of bone. Various subvolumes were made in each set--sacrum, ilium, ischium, lower pelvis, lumbosacral spine, sacrum, and whole pelvis--and compared for volume and DVH parameters (V(10), V(20), V(30), and V(40)) using paired t test. The hematological parameters during RT compiled from electronic database analyzed for higher than grade 2 (Radiation Therapy Oncology Group) HT and correlated with DVH parameters using log regression analysis (P < 0.05 significant). RESULTS: The FH subvolumes were 25% to 30% of WB. The mean DVH parameters V(10), V(20), V(30), and V(40) for whole-pelvis FH and WB were 86.5%, 77.5%, 62.5%, and 40.5%; and 88%, 79.6%, 62.9%, and 40%, respectively. There was significant difference between the DVH parameters of 2 sets (P < 0.05) for all subvolumes except ischium V(20), sacrum V(10), and lumbosacral spine V(10). The leukopenia, neutropenia, anemia, and thrombocytopenia higher than grade 2 was seen in 53%, 29.8%, 65.9%, and 10.6%, respectively. The mean V(10) for whole pelvis was less than 90% for both sets. On both univariate and multivariate analyses, only FH whole pelvis V(40) more than or equal to 40% correlated with higher than grade 2 leukopenia (Mann-Whitney U test, P = 0.026) and neutropenia (P = 0.05) with odds ratio, 4 (95% confidence interval, 1.166-13.728; P = 0.028). CONCLUSIONS: The FH bone marrow cavity volume is a better surrogate of active bone marrow on CT images and correlated with higher than grade 2 HT (V(40) >40%). Further prospective studies validating significance of high-dose effects and identifying correlation of bioimaging with CT contouring are warranted.

Predicting rectal and bladder overdose during the course of prostate radiotherapy using dose-volume data from initial treatment fractions.

PURPOSE: To evaluate whether information from the initial fractions can determine which patients are likely to consistently exceed their planning dose-volume constraints during the course of radiotherapy for prostate cancer. METHODS AND MATERIALS: Ten patients with high-risk prostate cancer were treated with helical tomotherapy to a dose of 60 Gy in 20 fractions. The prostate, rectum, and bladder were recontoured on their daily megavoltage computed tomography scans and the dose was recalculated. The bladder and rectal volumes (in mL) receiving ≥100% and ≥70% of the prescribed dose in each fraction and in the original plans were recorded. A fraction for which the difference between planned and delivered was more than 2 mL was considered a volume failure. Similarly if the difference in the planned and delivered maximum dose (D(max)) was ≥1% for the rectum and bladder, the fraction was considered a dose failure. Each patient's first 3 to 5 fractions were analyzed to determine if they correctly identified those patients who would consistently fail (i.e., ≥20% of fractions) during the course of their radiotherapy. RESULTS: Six parameters were studied; the rectal volume (RV) and bladder volumes (BV) (in mL) received ≥100% and ≥70% of the prescribed dose and maximum dose to 2 mL of the rectum and bladder. This was given by RV100, RV70, BV100, BV70, RD(max), and BD(max), respectively. When more than 1 of the first 3 fractions exceed the planning constraint as defined, it accurately predicts consistent failures through the course of the treatment. This method is able to correctly identify the consistent failures about 80% (RV70, BV100, and RV100), 90% (BV70), and 100% (RD(max) and BD(max)) of the times. CONCLUSIONS: This study demonstrates the feasibility of a method accurately identifying patients who are likely to consistently exceed the planning constraints during the course of their treatment, using information from the first 3 to 5 fractions.

Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation for conformal intracavitary brachytherapy in carcinoma of the uterine cervix.

PURPOSE: Trans-abdominal ultrasonography (US) is capable of determining size, shape, thickness, and diameter of uterus, cervix and disease at cervix or parametria. To assess the potential value of US for image-guided cervical cancer brachytherapy, we compared US-findings relevant for brachytherapy to the corresponding findings obtained from MR imaging. MATERIALS AND METHODS: Twenty patients with biopsy proven cervical cancer undergoing definitive radiotherapy with/without concomitant Cisplatin chemotherapy and suitable for brachytherapy were invited to participate in this study. US and MR were performed in a similar reproducible patient positioning after intracavitary application. US mid-sagittal and axial image at the level of external cervical os was acquired. Reference points D1 to D9 and distances were identified with respect to central tandem and flange, to delineate cervix, central disease, and external surface of the uterus. RESULTS: Thirty-two applications using CT/MR compatible applicators were evaluable. The D1 and D3 reference distances which represent anterior surface had a strong correlation with R=0.92 and 0.94 (p<0.01). The D2 and D4 reference distances in contrast, which represent the posterior surface had a moderate (D2) and a strong (D4) correlation with R=0.63 and 0.82 (p<0.01). Of all, D2 reference distance showed the least correlation of MR and US. The D5 reference distance representing the fundal thickness from tandem tip had a correlation of 0.98. The reference distances for D6, D7, D8, and D9 had a correlation of 0.94, 0.82, 0.96, and 0.93, respectively. CONCLUSIONS: Our study evaluating the use of US, suggests a reasonably strong correlation with MR in delineating uterus, cervix, and central disease for 3D conformal intracavitary brachytherapy planning.

Additional rectal and sigmoid mucosal points and doses in high dose rate intracavitary brachytherapy for carcinoma cervix: a dosimetric study.

BACKGROUND: Late rectal and sigmoid toxicities seen in cervical cancer patients are attributed to brachytherapy despite rectal doses within tolerance limits. The purpose of this study was to identify additional dosimetric points which may better forecast rectal complications. MATERIALS AND METHODS: Fifteen high dose rate intracavitary brachytherapy (ICA-HDR) applications with conventional X-ray and computed tomography (CT) based planning were studied. In addition to International Commission on Radiation Units and Measurement (ICRU) rectal and bladder points, proximal and distal rectal and sigmoid points were digitized on CT scans and dose volume histograms' (DVHs') parameters were computed and correlated. RESULTS: The mean ICRU, additional distal, proximal and sigmoid point doses were 486 ± 152 cGy, 527 ± 156 cGy, 401 ± 149 cGy and 838 ± 254 cGy, respectively, for a prescription of 700 cGy to point A. The mean sigmoid point dose was significantly higher than the ICRU rectal point doses (P=0.001). The high-dose sigmoid points were situated at a mean -8 mm (range -22.95 to 10.43 mm) lateral, 10 mm posterior (range -15.87 to 27.82 mm) and 31 mm (range 8.08-62.91 mm) cranial to the intracavitary applicator flange of central tandem. CONCLUSIONS: Our dosimetric study suggests that sigmoid points and 0.1 cm 3 receive significantly higher doses than rectal points during ICA-HDR in carcinoma of the uterine cervix. No definite conclusion on reproducible spatial distribution on orthogonal X-rays could be achieved. To document and reduce sigmoid doses, some form of 3D image-based planning is necessary.

Reporting and validation of gynaecological Groupe Euopeen de Curietherapie European Society for Therapeutic Radiology and Oncology (ESTRO) brachytherapy recommendations for MR image-based dose volume parameters and clinical outcome with high dose-rate brachytherapy in cervical cancers: a single-institution initial experience.

OBJECTIVE: The objectives are to report the dosimetric analysis, preliminary clinical outcome, and comparison with published data of 3-dimensional magnetic resonance-based high dose rate brachytherapy (BT) in cervical cancer. MATERIALS AND METHODS: The data set of 24 patients with cervical cancer treated with high dose-rate brachytherapy applications was analyzed. All patients received radiation with or without chemotherapy (10 patients received concomitant chemoradiation). Point A, International Commission on Radiation Units and Measurement (ICRU) point doses, and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology dose volume parameters, namely, high-risk clinical target volume (HR-CTV), D90 and D100 doses, and dose to D0.1cc and D2cc, for rectum, bladder, and sigmoid, were calculated and correlated. RESULTS: Mean ± SD HR-CTV was 45.2 ± 15.8 cc. The mean ± SD point A dose was 73.4 ± 4.5 Gy (median, 74.3 Gy) total biologically equivalent dose in 2 Gy per fraction (EQD2), whereas mean ± SD D90 doses were 70.9 ± 10.6 GyEQD2 (median, 68). The mean ± SD ICRU rectal and bladder points were 63.5 ± 8.1 and 80.4 ± 34.4 GyEQD2, respectively. The D0.1cc and D2cc for rectum were 66.0 ± 9.9 GyEQD2 (median, 64.5) and 57.8 ± 7.7 GyEQD2 (median, 58.8), for bladder 139.1 ± 54.7 GyEQD2 (median, 131.9) and 93.4 ± 24.6 GyEQD2 (median, 91), and sigmoid were 109.4 ± 45.2 GyEQD2 (median, 91) and 74.6 ± 19.6 GyEQD2 (median, 69.6). With a median follow-up of 24 months, 3 patients had local nodal failure, 1 had right external iliac nodal failure, and 1 had left supraclavicular nodal failure. CONCLUSIONS: The 3-D magnetic resonance image-based high dose-rate brachytherapy approach in cervical cancers is feasible. In our experience, the HR-CTV volumes are large, and D0.1cc and D2cc doses to bladder and sigmoid are higher than published literature so far.

'Plan of the day' adaptive radiotherapy for bladder cancer using helical tomotherapy.

BACKGROUND AND PURPOSE: This study assessed the potential of tomotherapy based Image Guided Radiotherapy (IGRT) to increase the accuracy of bladder irradiation using a 'plan of the day' adaptive radiotherapy (ART) technique. MATERIALS AND METHODS: Ten patients with muscle invasive bladder cancer underwent bladder preservation with trimodality therapy in an ongoing trial. All patients received 64 Gy/32# to the whole bladder and seven of them received a boost of 68 Gy/32# to the tumour bed. The ART technique entailed the generation of six IMRT plans for each patient, using six isotropic PTVs of 5-30 mm applied to the bladder volume (CTV) to generate the PTVs. Megavoltage CT (MVCT) imaging was done to correct positioning errors and choose the 'plan of the day'. RESULTS: Post treatment MVCT scans (315 scans) were used to generate multiple anisotropic PTVs for three hypothetical scenarios. Overall, coverage of anterior and superior walls required larger margins than other walls. Maximum geographical miss, in spite of IGRT, was noted for the superior (13.8%) and anterior walls (10.3%). CONCLUSIONS: Plan of the day ART is a feasible and promising technique for optimal treatment and dose escalation in bladder cancer.