Late urinary toxicity and QOL with pelvic radiotherapy for high-risk prostate cancer: Dose-effect relations in the POP-RT randomized phase III trial.

PURPOSE: The POP-RT phase III randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiotherapy (WPRT) versus prostate-only radiotherapy (PORT) for high/very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. MATERIALS/METHODS: Late urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65Gy, V68Gy) in the approved radiotherapy plans was compared for urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. RESULTS: Complete combined data for late urinary symptoms and dosimetry was available for 193/224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for WPRT and PORT (5.2% vs 4.1%, p=0.49), while grade 2 toxicity was 31.3% vs 22.7% respectively (p=0.12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior TURP, grade 2+ acute urinary toxicity, low bladder dose (V10Gy) and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. CONCLUSION: Over long term follow up, whole pelvic radiotherapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiotherapy. The long term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Dosimetric Impact of Voluntary Deep Inspiration Breath Hold (DIBH) in Mediastinal Hodgkin Lymphomas: A Comparative Evaluation of Three Different Intensity Modulated Radiation Therapy (IMRT) Delivery Methods Using Voluntary DIBH and Free Breathing Techniques.

Hodgkin lymphomas are radiosensitive and curable tumors that often involve the mediastinum. However, the application of radiation therapy to the mediastinum is associated with late effects including cardiac and pulmonary toxicities and secondary cancers. The adoption of conformal IMRT and deep inspiration breath- hold (DIBH) can reduce the dose to healthy normal tissues (lungs, heart and breast). We compared the dosimetry of organs at risk (OARs) using different IMRT techniques for two breathing conditions, i.e., deep inspiration breath hold (DIBH) and free breathing. Twenty-three patients with early-stage mediastinal Hodgkin lymphomas were accrued in the prospective study. The patients were given treatment plans which utilized full arc volumetric modulated arc therapy (F-VMAT), Butterfly VMAT (B-VMAT), and fixed field IMRT (FF-IMRT) techniques for both DIBH and free breathing methods, respectively. All the plans were optimized to deliver 95% of the prescription dose which was 25.2 Gy to 95% of the PTV volume. The mean dose and standard error of the mean for each OAR, conformity index (CI), and homogeneity index (HI) for the target using the three planning techniques were calculated and compared using Student's t-test for parametric data and Wilcoxon signed-rank test for non-parametric data. The HI and CI of the target was not compromised using the DIBH technique for mediastinal lymphomas. The mean values of CI and HI for both DIBH and FB were comparable. The mean heart doses were reduced by 2.1 Gy, 2.54 Gy, and 2.38 Gy in DIBH compared to FB for the F-VMAT, B-VMAT, and IMRT techniques, respectively. There was a significant reduction in V5Gy, V10Gy, and V15Gy to the heart (p < 0.005) with DIBH. DIBH reduced the mean dose to the total lung by 1.19 Gy, 1.47 Gy, and 1.3 Gy, respectively. Among the 14 female patients, there was a reduction in the mean right breast dose with DIBH compared to FB (4.47 Gy vs. 3.63 Gy, p = 0.004). DIBH results in lower heart, lung, and breast doses than free breathing in mediastinal Hodgkin Lymphoma. Among the different IMRT techniques, FF-IMRT, B-VMAT, and F-VMAT showed similar PTV coverage, with similar conformity and homogeneity indices. However, the time taken for FF-IMRT was much longer than for the F-VMAT and B-VMAT techniques for both breathing methods. B-VMAT and F-VMAT emerged as the optimal planning techniques able to achieve the best target coverage and lower doses to the OARs, with less time required to deliver the prescribed dose.

Development and Validation of Single-Optimization Knowledge-Based Volumetric Modulated Arc Therapy Model Plan in Nasopharyngeal Carcinomas.

Purpose: Knowledge-based planning (KBP) has evolved to standardize and expedite the complex process of radiation therapy planning for nasopharyngeal cancer (NPC). Herein, we aim to develop and validate the suitability of a single-optimization KBP for NPC. Methods and Materials: Volumetric modulated arc therapy plans of 103 patients with NPC treated between 2016 and 2020 were reviewed and used to generate a KBP model. A validation set of 15 patients was employed to compare the quality of single optimization KBP and clinical plans using the paired t test and the Wilcoxon signed rank test. The time required for either planning was also analyzed. Results: Most patients (86.7%) were of locally advanced stage (III/IV). The median dose received by 95% of the high-risk planning target volume was significantly higher for the KBP (97.1% vs 96.4%; P = .017). The median homogeneity (0.09 vs 0.1) and conformity (0.98 vs 0.97) indices for high-risk planning target volume and sparing of the normal tissues like optic structures, spinal cord, and uninvolved dysphagia and aspiration-related structures were better with the KBP (P < .05). In the blinded evaluation, the physician preferred the KBP plan in 13 out of 15 patients. The median time required to generate the KBP and manual plans was 53 and 77 minutes, respectively. Conclusions: KBP with a single optimization is an efficient and time saving alternative for manual planning in NPC.

Can knowledge based treatment planning of VMAT for post-mastectomy locoregional radiotherapy involving internal mammary chain and supraclavicular fossa improve performance efficiency?

Introduction: To validate and evaluate the performance of knowledge-based treatment planning for Volumetric Modulated Arc Radiotherapy for post-mastectomy loco-regional radiotherapy. Material and methods: Two knowledge-based planning (KBP) models for different dose prescriptions were built using the Eclipse RapidPlanTM v 16.1 (Varian Medical Systems, Palo Alto, USA) utilising the plans of previously treated patients with left-sided breast cancer who had undergone irradiation of the left chest wall, internal mammary nodal (IMN) region and supra-clavicular fossa (SCF). Plans of 60 and 73 patients were used to generate the KBP models for the prescriptions of 40 Gy in 15 fractions and 26 Gy in 5 fractions, respectively. A blinded review of all the clinical plans (CLI) and KBPs was done by two experienced radiation oncology consultants. Statistical analysis of the two groups was also done using the standard two-tailed paired t-test or Wilcoxon signed rank test, and p<0.05 was considered significant. Results: A total of 20 metrics were compared. The KBPs were found to be either better (6/20) or comparable (10/20) to the CLIs for both the regimens. Dose to heart, contralateral breast,contralateral lung were either better or comparable in the KBP plans except of ipsilateral lung. Mean dose (Gy) for the ipsilateral lung are significantly (p˂0.001) higher in KBP though the values were acceptable clinically. Plans were of similar quality as per the result of the blinded review which was conducted by slice-by-slice evaluation of dose distribution for target coverage, overdose volume and dose to the OARs. However, it was also observed that treatment times in terms of monitoring units (MUs) and complexity indices are more in CLIs as compared with KBPs (p<0.001). Discussion: KBP models for left-sided post-mastectomy loco-regional radiotherapy were developed and validated for clinical use. These models improved the efficiency of treatment delivery as well as work flow for VMAT planning involving both moderately hypo fractionated and ultra-hypo fractionated radiotherapy regimens.

Optimizing Target Volume for Adjuvant Radiation Therapy in Penile Cancer.

PURPOSE: Recent studies have reported improved outcomes with adjuvant radiation therapy in penile cancer. However, the appropriate target volumes to be irradiated in this group of patients for optimal outcomes are still unclear. This study aims to report the patterns of failure and define target volumes to be irradiated in patients with pN3 penile cancer. METHODS AND MATERIALS: Patients with pT1-T4, pN3, cM0, and squamous cell carcinoma of the penis who received adjuvant radiation therapy (involved field or extended field), with or without concurrent chemotherapy were included in the study. Complete information on disease characteristics, radiation therapy target details, and patterns of failure were available for 75 patients. Disease-free (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and log-rank test was used to compare survival outcomes between the involved field and extended field radiation therapy groups. Multivariate analysis was performed using the Cox proportional hazards model to analyze factors correlating with survival outcomes. RESULTS: At a median follow-up of 39 months, 38.6% (29/75) of patients had relapsed either locally, regionally, or at distant sites. Of the 24 patients who received extended field radiation therapy (EFRT), only 1 (4%) patient experienced relapse. Twenty-eight (55%) patients experienced relapse after involved-field radiation therapy (IFRT), of which 28.5% were regional-only relapses and 64% relapses were associated with a regional component. The 2-year DFS and OS of the entire cohort were 62.2% and 70.8%, respectively. The 2-year DFS was 67.9% in patients who received IFRT and 94.1% in those who received EFRT (P = .002), and the 2-year OS was 62.4% with IFRT and 91.1% with EFRT (P = .014). Extended field radiation therapy was associated with an improved DFS (hazard ratio, 12.2; 95% confidence interval, 1.5-97.4; P = .02) and OS (hazard ratio, 4.6; 95% confidence interval, 1-21.5; P = .05) on multivariate analysis. CONCLUSIONS: Extended field radiation therapy significantly improves clinical outcomes compared with involved-field radiation in patients with pN3 penile cancer.

Quantitative Comparison of Dosimetric Data Between the Indigenous Baseplate and Commercially Available Carbon Fiber Baseplate for 6 and 15 MV Photon Energy.

Background: This study aims to design an indigenous baseplate (ID baseplate) that is economically viable and dosimetrically comparable for radiotherapy patient treatment. An ID baseplate was designed and manufactured using wood plastic composition materials that are readily available in the market and were compared dosimetrically with the commercially available carbon fiber baseplate (CF baseplate). Materials and Methods: Surface dose and beam attenuation properties of both the baseplates (ID and CF) were measured using a parallel plate chamber and compared with the dose calculated from the treatment planning system (TPS). Separate computer tomography images of both the baseplates were acquired by placing solid water phantoms. These images were used for surface dose calculation in the TPS and were validated with experimental measurements. Proper densities were assigned to the couch and baseplates to avoid uncertainties in dose calculations. All measurements were performed at field sizes 10 cm × 10 cm for 6 MV and 15 MV photon beams. Results: The percentage surface dose measured for the ID baseplate and CF baseplate was found to be matching for 6 MV beam (98.2% and 97%, respectively); however, for the 15 MV beam, the ID baseplate showed a higher surface dose of 98.6% compared to CF baseplate (87.4%). For the ID baseplate, the percentage difference in the surface dose between that TPS calculated value and the measured values were 1.6% and 1.4% for 6MV and 15MV, respectively. The ID baseplate showed higher beam attenuation than the CF baseplate by 2.2% for the 6MV beam and 3.4% for the 15MV beam when proper electron densities were not assigned. The difference between the TPS calculated dose and delivered dose was achieved within 3% after assigning proper electron density to the couch and baseplate. Conclusions: The ID baseplate has shown acceptable dosimetric results and can be an economically viable alternative to the commercially available CF baseplates. The manufacturing cost of the ID baseplate was ten times cheaper than the CF baseplate.

Common Iliac Node-Positive Prostate Cancer Treated With Curative Radiation Therapy: N1 or M1a?

PURPOSE: Common iliac (CI) nodes are staged as (oligo)metastatic M1a for prostate cancer. Whether outcomes of pelvic node-positive (cN1) differ from CI node-positive (CI-M1a) prostate cancer after curative treatment is unclear. The present study compares outcomes in patients treated with radical whole pelvic radiation therapy (RT) and long-term androgen deprivation therapy (ADT). METHODS AND MATERIALS: Patients with a node-positive adenocarcinoma prostate were identified, either CI-M1a or cN1, from a prospectively maintained database. More than 75% of patients were staged with Gallium (Ga) 68 prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) at the time of diagnosis. All patients received long-term ADT and moderately or extremely hypofractionated RT to the prostate and pelvis, including the CI region. At the time of biochemical failure (BCF), restaging was done with Ga68-PSMA-PET/CT to establish the patterns of failure. The CI-M1a cohort was classified as proximal or distal CI nodal location, and studied for outcomes. RESULTS: Of the 130 patients analyzed, 87 had cN1 and 43 had CI-M1a stage disease. The median duration of ADT before RT was 7 months, and total duration was at least 24 months. The majority of patients (65%) had Gleason grade group IV to V, and 75% had ≥T3 disease. After a median follow up of 61 months, BCF in the 2 groups was similar (cN1: n = 21 of 87; 24.1%; CI-M1a: n = 11 of 43; 25.6%; P = .86). At the time of BCF, restaging Ga68-PSMA-PET/CT located distant metastases in 20 of 32 patients (63%; 57% in cN1 and 73% in CI-M1a; P = .47). In addition, the 5-year biochemical failure-free (cN1: 77.4%; CI-M1a: 70.4%; P = .43), distant metastasis-free (cN1: 86.9%; CI-M1a: 79.4%; P = .23), and overall (cN1: 92.6%; CI-M1a 90.1%; P = .80) survival were similar in the 2 groups. Outcomes within CI-M1a were similar for proximal versus distal CI nodal location and 5-year biochemical failure-free survival (73.6% vs 58.6%; P = .81). CONCLUSIONS: Patients with oligometastatic CI-M1a and cN1 prostate cancer showed similar outcomes when treated with curative whole pelvic RT and long-term ADT. The treatment for these oligometastatic patients should be prospectively evaluated.

Acute and Late Adverse Effects of Prostate-Only or Pelvic Stereotactic Radiation Therapy in Prostate Cancer: A Comparative Study.

PURPOSE: To compare the urinary and gastrointestinal adverse effects with or without the inclusion of pelvic nodal regions in patients treated with extreme hypofractionated stereotactic radiation therapy (SBRT) for prostate cancer. METHODS AND MATERIALS: Patients treated with definitive SBRT for nonmetastatic adenocarcinoma prostate were identified from prospectively maintained institutional database, and details of radiation therapy volume, dose, acute, and late adverse effects were analyzed. Symptoms of acute (within 90 days of completing SBRT) and late gastrointestinal and urinary toxic effects were graded using Common Terminology Criteria for Adverse Effects version 5.0. Each symptom was scored according to the worst reported grading during treatment and the follow-up period. Cumulative rates of adverse effects between prostate-only SBRT (PO-SBRT) and whole pelvic SBRT (WP-SBRT) were compared using the χ2 test. Univariable and multivariable analysis was performed for possible factors affecting acute gastrointestinal and late urinary toxic effects. RESULTS: A total of 220 patients were analyzed (PO-SBRT = 118, WP-SBRT = 102), with a median follow-up of 28 months (interquartile range, 14-40). Most patients had locally advanced disease (PO-SBRT 60% high risk and 40% intermediate risk, WP-SBRT 79% node positive, and 21% high risk). The median SBRT dose was 36.25Gy (interquartile range, 35-36.25) to the prostate (2-Gy equivalent, EQD2 = 90.6Gy, a/b = 1.5Gy) and simultaneous integrated 25Gy to the pelvis (EQD2 = 46.3Gy) in 5 fractions on alternate days. No grade 3 to 4 acute adverse effects were observed except 1 grade 3 urinary obstruction (PO-SBRT). WP-SBRT was associated with a significantly higher rate of acute grade 2 gastrointestinal toxic effects (29.4% vs 14.7%, P = .008) and late grade 2 urinary adverse effects (45.6% vs 25.0%, P = .003). Both groups had low incidence of late grade 3 adverse effects (urinary 2.5%, gastrointestinal 1%). CONCLUSIONS: WP-SBRT was associated with significantly higher acute gastrointestinal and late urinary adverse effects compared with PO-SBRT, although overall incidence of severe adverse effects was low.

Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial.

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial.

PURPOSE: We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer. METHODS: This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52; P < .0001). WPRT also showed higher 5-year DFS (89.5% v 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; P = .002), but 5-year OS did not appear to differ (92.5% v 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; P = .83). Distant metastasis-free survival was also higher with WPRT (95.9% v 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; P = .01). Benefit in BFFS and DFS was maintained across prognostic subgroups. CONCLUSION: Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ.

Temporal course of late rectal toxicity & impact of intervention in patients undergoing radiation for cervical cancer.

BACKGROUND & OBJECTIVES: : There is limited information available on the temporal course of late stage radiotherapy adverse effects. The present study reports on the temporal course of late toxicities after chemoradiation and brachytherapy. METHODS: : Women with cervical cancer who presented with late toxicity after (chemo) radiation were included in the study. Grade of toxicity (Clinical Toxicity Criteria for Adverse Events version 4.03) and type of intervention were recorded at three-monthly interval for the first year and then six monthly until 24 months. Direct cost for the management of toxicity was calculated. Univariate analysis was performed to understand the impact of various factors on persistence of toxicity. RESULTS: : Ninety two patients were included in this study. Grades I, II, III and IV toxicities were observed in 50 (54%), 33 (36%), 7 (8%) and 2 (2%) patients, respectively, at first reporting. Patients spent a median of 12 (3-27) months with toxicity. At 12 months, 48/92 (52.2%) patients had a complete resolution of toxicity, whereas 27/92 (29.3%) patients had low grade (I-II) persistent toxicity. Only 6/92 (6.5%) patients who had grade III-IV toxicity had resolution to a lower grade. Four (4.3%) patients died due to toxicity. At 24 months, 9 (10%) patients continued to have grade ≥ III toxicity. On an average, 7 (2-24) interventions were required for the clinical management of late toxicity and median direct cost incurred was ₹ 50,625 (1,125-303,750). INTERPRETATION & CONCLUSIONS: : In this study late radiation toxicity resolved within 12 months in more than half of patients. However, others are likely to have had persistent lower grade toxicity or progression to higher grade. Structured strategies are hence needed for the effective management of late toxicities.

Intensity-modulated radiation therapy versus three-dimensional conformal radiotherapy in head and neck squamous cell carcinoma: long-term and mature outcomes of a prospective randomized trial.

PURPOSE: To compare long-term disease-related outcomes and late radiation morbidity between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in head and neck squamous cell carcinoma (HNSCC) in the setting of a prospective randomized controlled trial. METHODS: Previously untreated patients with early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx (T1-T3, N0-N2b, M0) planned for comprehensive irradiation of primary site and bilateral neck nodes were randomly assigned to either IMRT or 3D-CRT after written informed consent. Patients were treated with 6MV photons to a total dose of 70Gy/35 fractions over 7 weeks (3D-CRT) or 66Gy/30 fractions over 6 weeks (IMRT). A sample size of 60 patients was estimated to demonstrate 35% absolute difference in the incidence of ≥grade 2 acute xerostomia between the two arms. All time-to-event outcomes were calculated from date of randomization until the defined event using the Kaplan-Meier method. RESULTS: At a median follow-up of 140 months for surviving patients, 10-year Kaplan-Meier estimates of loco-regional control (LRC); progression-free survival (PFS); and overall survival (OS) with 95% confidence interval (95%CI) were 73.6% (95%CI: 61.2-86%); 45.2% (95%CI: 32-58.4%); and 50.3% (95%CI: 37.1-63.5%) respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRC [79.2% (95%CI: 62.2-96.2%) vs 68.7% (95%CI: 51.1-86.3%), p = 0.39]; PFS [41.3% (95%CI: 22.3-60.3%) vs 48.6% (95%CI: 30.6-66.6%), p = 0.59]; or OS [44.9% (95%CI: 25.7-64.1%) vs 55.0% (95%CI: 37-73%), p = 0.49]. Significantly lesser proportion of patients in the IMRT arm experienced ≥grade 2 late xerostomia and subcutaneous fibrosis at all time-points. However, at longer follow-up, fewer patients remained evaluable for late radiation toxicity reducing statistical power and precision. CONCLUSIONS: IMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC.

Defining dose constraints for catheter insertion sites to minimize toxicity after interstitial breast brachytherapy.

PURPOSE: The purpose of this study was to define dose constraints for catheter insertion sites to minimize probability of prominent post-therapy skin marks after interstitial breast brachytherapy. METHODS AND MATERIALS: Forty patients who had undergone interstitial breast brachytherapy were studied at followup at least 2 years after the procedure. Their implant marks were compared with background skin and areola and scored as Gr0 = invisible (same color as surrounding skin), Gr1 = darker than surrounding skin but lighter than areola or hypopigmentation, and Gr2 = same color as areola or darker. Highest point doses received in each plane of implant and their corresponding closest distances from clinical target volume, 85% isodose, and closest catheter dwell point were used for analysis. A logistic regression was performed to ascertain effects of various dosimetric parameters on the probability of Gr2 marks. Receiver operating characteristic curve was generated to derive cutoffs. RESULTS: A total of 280 dose points were studied. Median values for various parameters were 1.4 Gy (0.24-3.74) for Dose max and 1.6 cm, 1.5 cm, and 1.0 cm for Dist CTV min, Dist Iso min, and Dist Dwell min, respectively. On logistic regression, increasing Dose max alone was associated with an increased likelihood of developing Gr2 marks. Each unit increase of Dose max increased probability of development of Gr2 skin marks by 5.0% (2.391-10.328). Receiver operating characteristic analysis also showed greatest odd ratio (8.0), sensitivity (74.8%), and specificity (73%) for Dose max. CONCLUSIONS: It seems prudent to restrict dose to catheter insertion sites for better cosmesis.

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.

Commissioning and validation of commercial deformable image registration software for adaptive contouring.

PURPOSE: To report the commissioning and validation of deformable image registration(DIR) software for adaptive contouring. METHODS: DIR (SmartAdapt®v13.6) was validated using two methods namely contour propagation accuracy and landmark tracking, using physical phantoms and clinical images of various disease sites. Five in-house made phantoms with various known deformations and a set of 10 virtual phantoms were used. Displacement in lateral, anterio-posterior (AP) and superior-inferior (SI) direction were evaluated for various organs and compared with the ground truth. Four clinical sites namely, brain (n = 5), HN (n = 9), cervix (n = 18) and prostate (n = 23) were used. Organs were manually delineated by a radiation oncologist, compared with the deformable image registration (DIR) generated contours. 3D slicer v4.5.0.1 was used to analyze Dice Similarity Co-efficient (DSC), shift in centre of mass (COM) and Hausdorff distances Hf95%/avg. RESULTS: Mean (SD) DSC, Hf95% (mm), Hfavg (mm) and COM of all the phantoms 1-5 were 0.84 (0.2) mm, 5.1 (7.4) mm, 1.6 (2.2) mm, and 1.6 (0.2) mm respectively. Phantom-5 had the largest deformation as compared to phantoms 1-4, and hence had suboptimal indices. The virtual phantom resulted in consistent results for all the ROIs investigated. Contours propagated for brain patients were better with a high DSC score (0.91 (0.04)) as compared to other sites (HN: 0.84, prostate: 0.81 and cervix 0.77). A similar trend was seen in other indices too. The accuracy of propagated contours is limited for complex deformations that include large volume and shape change of bladder and rectum respectively. Visual validation of the propagated contours is recommended for clinical implementation. CONCLUSION: The DIR algorithm was commissioned and validated for adaptive contouring.

First clinical report of helical tomotherapy with simultaneous integrated boost for synchronous bilateral breast cancer.

OBJECTIVE: Radiotherapy (RT) for synchronous bilateral breast cancer (SBBC) is technically very challenging. This study reports the clinical feasibility, dosimetry and safety of helical tomotherapy (HT) with simultaneous integrated boost (SIB) in patients treated with adjuvant radiotherapy for SBBC. METHODS: 21 women with SBBC treated with HT from January 2013 to June 2016 were retrospectively evaluated. Radiation lung toxicity was assessed using pulmonary function test (PFT) and high-resolution computerized tomography scan (HRCT) scan at baseline and 1 yearpost-RT in 18 patients. Survival was calculated using Kaplan-Meier curves. Significance of the difference between pre- and post-RT PFT values was assessed using paired t-test. RESULTS: The dose prescription was 50Gy to the breast, chest wall or regional nodes and 61Gy to the tumour bed as SIB, delivered in 25 fractions. Dosimetric outcome was excellent both for target volumes and normal tissues. Acute skin and oesophageal toxicities were minimal. Symptomatic radiation-induced pnuemonitis was not observed. Subclinical radiological Grade I-II changes were apparent in 14 patients. Only one patient developed Grade III radiological change whereas no change was documented for three patients. PFTs did not show any significant change in any of the measured parameters. At a median follow-up of 25 months, 3-year disease-free survival, overall survival and loco-regional control were 65.6%, 83.3% and 85.7% respectively. CONCLUSION: Women with SBBC can be safely treated with HT and this is not associated with adverse short- to intermediate term radiation toxicity. Advances in knowledge: This is the first report that establishes the safety of HT for adjuvant RT using SIB technique in SBBC.

Multi-catheter interstitial brachytherapy for partial breast irradiation: an audit of implant quality based on dosimetric evaluation comparing intra-operative versus post-operative placement.

PURPOSE: The use of multicatheter interstitial brachytherapy (MIB) for accelerated partial breast irradiation (APBI) in early breast cancer (EBC) patients outside the trial setting has increased. Hence, there is a need to critically evaluate implant quality. Moreover, there is a scarcity of reports using an open cavity technique. We report the dosimetric indices of open and closed cavity MIB techniques. MATERIAL AND METHODS: The dosimetric parameters of 60 EBC patients treated with MIB (open and closed cavity) who underwent three dimensional, computerized tomography (CT) based planning for APBI from November 2011 to July 2015 were evaluated. Coverage Index (CI), Dose Homogeneity Index (DHI), Conformity Index (COIN), Plan Quality Index (PQI), and Dose Non-uniformity Index (DNR) were assessed. RESULTS: Forty-one patients underwent open cavity and 19 patients underwent closed cavity placement of brachytherapy catheters. The median number of planes was 4 and median number of needles was 20. Median dose was 34 Gy with dose per fraction of 3.4 Gy, given twice a day, 6 hours apart. The D90 of the cavity and clinical target volume (CTV) were 105% and 89%, respectively. The median doses to the surgical clips were greater than 100%. The median CI of the cavity and CTV was 0.96 and 0.82, respectively. The DHI and COIN index of the CTV was 0.73 and 0.67. There were no significant differences in the dosimetric parameters based on whether the technique was done open or closed. CONCLUSIONS: Critical evaluation of the dosimetric parameters of MIB-APBI is important for optimal results. While the open and closed techniques have similar dosimetry, our institutional preference is for an open technique which eases the procedure due to direct visualization of the tumor cavity.