A dose escalated fiducial marker-based image guided radical radiotherapy in locally advanced prostate cancers: A single institute experience from India.

Purpose: Image guided radiotherapy (IGRT) is one of the most commonly used treatment in LAPC. Dose escalation >74 Gy has shown to improve the biochemical control and freedom from failure rate in LAPC.We started treating LAPC patients with dose escalated IGRT in our institute since 2008. We did a retrospective analysis to see the biochemical relapse-free survival, cancer-specific survival, and bladder and rectal toxicity. Methods: A total of 50 consecutive prostate cancer patients were treated with dose escalated IGRT between January 2008 to Dec 2013. Out of these, 37 patients of LAPC were analyzed and their medical records were retrieved. All were biopsy proven adenocarcinoma of prostate with D'Amico high risk category (PSA >20 ng/mL or Gleason score (GS) >7 or T2c-T4). Three gold fiducial markers were placed in the prostate. Patients were immobilized in supine position with either ankle or knee rest. Partial bladder filling and rectum emptying protocol was followed. Clinical target volume (CTV) segmentation was done according to EORTC recommendation. Population based PTV expansion from CTV of 10 mm (cranio-caudal), 10 mm (medio-lateral), 10 mm (anterior) and 5 mm (posterior) was given. In patients with radiologically enlarged pelvic lymph node, whole pelvis intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy/28# followed by prostatic boost 26Gy/13# by IMRT using image guidance. Rest of the patients received prostate only RT to a dose of 76Gy/38# by IGRT. Daily On board KV images were taken and 2D-2D fiducial marker matching was done and shifts were applied on machine before treatment. Biochemical relapse was defined as per Phoenix definition (nadir + 2 ng/mL). Radiation Therapy Oncology Group (RTOG) toxicity grading system was used to document acute and late toxicity. Results: Median age of patients was 66 years. Median pre-treatment PSA was 22 ng/mL. Thirty patients (81%) had T3/T4 lesions and nodal metastasis was seen in 11 (30%). Median GS was 8. Median radiotherapy dose was 76 Gy. Imaging before radiation delivery was done in 19(51%) patients and 100% in 14 (38%) patients. With a median follow up of 6.5 years, 5-year biochemical relapse-free survival (bRFS) and cancer-specific survival (CSS) was 66% and 79% respectively. Mean bRFS and CSS were 71 months and 83 months however Median bRFS and CSS were not reached. Distant metastasis was seen in 8 (22%). RTOG grade III bladder and rectal toxicity was seen in 2 (6%) and 2 (6%) patients respectively. Conclusion: Dose escalated IGRT with fiducial marker positional verification for LAPC is doable in Indian setup provided more emphasis given on daily on-board imaging with rigorous bladder filling and rectal emptying protocol. Long term follow up is needed to assess the effect on distant disease-free survival and CSS.

Consolidation chemoradiation (cCTRT) improves survival in responders to first-line chemotherapy (CT) in locally advanced gallbladder cancer (LA-GBC): A new standard of care?

Introduction: Chemotherapy (CT) is the standard of care in advanced gallbladder cancer (GBC). Should locally advanced GBC (LA-GBC) with response to CT and good performance status (PS) be offered as consolidation chemoradiation (cCTRT) to delay progression and improve survival? There is a scarcity of literature on this approach in the English literature. We present our experience with this approach in LA-GBC. Materials and Methods: After obtaining ethics approval, we reviewed the records of consecutive GBC patients from 2014 to 2016. Out of 550 patients, 145 were LA-GBC who were initiated on chemotherapy. A contrast-enhanced computed tomography (CECT) abdomen was done to evaluate the response to treatment, according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. All responders to CT (PR and SD) with good PS but unresectable were treated with cCTRT. Radiotherapy was given to GB bed, periportal, common hepatic, coeliac, superior mesenteric, and para-aortic lymph nodes up to a dose of 45 to 54 Gy in 25 to 28 fractions along with concurrent capecitabine at the rate of 1,250 mg/m2. Treatment toxicity, overall survival (OS), and factors affecting OS were computed based on Kaplan-Meier and Cox regression analysis. Results: ">The median age of patients was 50 years (interquartile range [IQR] = 43-56 years), and men to women ratio was 1:3. A total of 65% and 35% patients received CT and CT followed by cCTRT, respectively. The incidence of Grade 3 gastritis and diarrhea was 10% and 5%, respectively. Responses were partial response (PR; 65%), stable disease (SD; 12%), progressive disease (PD; 10%), and nonevaluable (NE; 13%) because they did not complete six cycles of CT or were lost to follow-up. Among PR, 10 patients underwent radical surgery (six after CT and four after cCTRT). At a median follow-up of 8 months, the median OS was 7 months with CT and 14 months with cCTRT (P = 0.04). The median OS was 57 months, 12 months, 7 months, and 5 months for complete response (CR) (resected), PR/SD, PD, and NE (P = 0.008), respectively. OS was 10 months and 5 months for Karnofsky performance status (KPS) >80 and <80 (P = 0.008), respectively. PS (hazard ratio [HR] = 0.5), stage (HR = 0.41), and response to treatment (HR = 0.05) were retained as independent prognostic factors. Conclusions: CT followed by cCTRT appears to improve survival in responders with good PS.

Cardiac dose reduction using deep inspiratory breath hold (DIBH) in radiation treatment of left sided breast cancer patients with breast conservation surgery and modified radical mastectomy.

PURPOSE: Deep inspiration breath hold (DIBH) reduces heart and pulmonary doses during left-sided breast radiation therapy (RT); however, there is limited information whether the reduction in doses is similar in patients with modified radical MRM (MRM) and breast conservation surgery (BCS). The primary objective was to determine whether DIBH offers greater dosimetric reduction in cardiac doses in patients with MRM as compared to BCS with secondary objectives of documenting time consumed in counseling, simulation and planning such techniques. METHODS: Thirty patients with diagnosis of left sided breast cancer underwent CT simulation both free breathing (FB) and DIBH. Patients were grouped into two cohorts: MRM (n = 20) and BCS (n = 10). 3D-conformal plans were developed and FB was compared to DIBH for entire group (n = 30) and each cohort using Wilcoxon signed-rank tests for continuous variables and McNemar's test for discrete variables. The percent relative reduction conferred by DIBH in mean heart (Dmean heart) and left anterior descending artery dose (LADmean and LADmax), heart V25,V10, V2 and ipsilateral DmeanLung,V20, V12 were compared between the two cohorts using Wilcox rank-sum testing. A two-tailed p-value ≤ 0.05 was considered statistically significant. Time consumed during FB and DIBH from patient counseling to planning was documented. RESULTS: Patients undergoing BCS had comparable boost target coverage on DIBH and FB. For the overall group (n = 30), DIBH reduced Dmean heart and LAD dose, V25, V10 and V2 doses for the heart and Ipsilateral DmeanLung, V20, V12 which was statistically significant. For individual cohorts DIBH did not significantly reduce the lung (Ipsilateral DmeanLung, V20, V12) and LAD (LADmean and LADmax) doses for BCS while significant reduction in all cardiopulmonary doses was seen in MRM cohort. Despite significant reductions with DIBH in MRM, ipsilateral lung constraint of V12 < 15% was less commonly achieved in MRM (n = 11, 55%) requiring nodal radiation as compared to BCS (n = 3, 30%). Percent reduction in all cardiac and pulmonary dosimetric parameters with DIBH was similar in the MRM cohort as compared to BCS cohort. In total 73.1 ± 2.6 min was required for FB as compared to 108.1 ± 4.1 min in DIBH. CONCLUSION: DIBH led to significant reduction of cardiac doses in both MRM and BCS. Reduction of lung and LAD doses were significant in MRM cohort. All cardiac constraints were met with DIBH in both cohorts, lung constraints were less frequently met in MRM cohort requiring nodal radiation.

Comparison of set-up errors by breast size on wing board by portal imaging.

AIM: To quantify and compare setup errors between small and large breast patients undergoing intact breast radiotherapy. METHODS: 20 patients were inducted. 10 small/moderate size breast in arm I and 10 large breast in arm II. Two orthogonal and one lateral tangent portal images (PIs) were obtained and analyzed for systematic (Σ) and random (σ) errors. Effect of no action level (NAL) was also evaluated retrospectively. RESULTS: 142 PIs were analyzed. Σ(mm) was 3.2 versus 6.7 (p = 0.41) in the mediolateral (ML) direction, 2.1 versus 2.9 (p = 0.06) in the craniocaudal (CC) and 2.2 versus 3.6 (p = 0.08) in the anteroposterior (AP) direction in small and large breast, respectively. σ(mm) was 3.0, 3.3 and 3.3 for small breast and 4.1, 3.7 and 3.2 for large breast in the ML, CC and AP direction (p = 0.07, 0.86, 0.37), respectively. 3 D Σ(mm) was 2.7 versus 4.2 (p = 0.01) and σ(mm) was 2.5 versus 3.2 (p = 0.14) in arm I and II, respectively. The standard deviation (SD) of variations (mm) in breast contour depicted by central lung distance (CLD) was 5.9 versus 7.4 (p < 0.001), central flash distance (CFD) 6.6 versus 10.5 (p = 0.002), inferior central margin (ICM) 4 versus 4.9 (p < 0.001) in arm I and II, respectively. NAL showed a significant reduction of systematic error in large breast in the mediolateral direction only. CONCLUSION: Wing board can be used in a busy radiotherapy department for setting up breast patients with a margin of 1.1 cm, 0.76 cm and 0.71 cm for small breasts and 1.96 cm, 1.12 cm and 0.98 cm for large breast in the ML, AP and CC directions, respectively. The large PTV margin in the mediolateral direction in large breast can be reduced using NAL. Further research is needed to optimize positioning of large breasted women.

Is aspiration as detected on pretreatment video fluorography, a harbinger of poor quality of life and early mortality in cancers of the upper aerodigestive tract treated with radiotherapy?

BACKGROUND: Patients with cancers of the upper aerodigestive tract (head and neck cancer (HNC)) tend to aspirate, either due to disease or treatment. The association of aspiration (documented on video fluorography (VFG)) with quality of life (QOL) and unexpected mortality was studied prospectively in patients treated with simultaneous integrated boost technique of intensity-modulated radiotherapy (SIB-IMRT). MATERIALS AND METHODS: Moderately advanced (stage III/IV) HNC were treated by SIB-IMRT delivering 66 Gy/30 fr, 60 Gy/30 fr, and 54 Gy/30 fr to high, intermediate, and low risk volumes, respectively. They underwent serial VFG and QOL assessments (Quality of Life Questionnaire-Core 30 (QLQ-C30) and head and neck-35 (HN35) European Organisation for Research and Treatment of Cancer (EORTC) tools) at 0, 3, and 6 months. Pharyngeal musculature (PM) was additionally delineated on planning computed tomography (CT) scans as potential organs at risk (OARs). RESULTS: Between November 2009 and May 2011, 20 HNC were treated as per protocol. All patients were fit (Karnofsky performance status (KPS) ≥ 80). Based on VFG findings, seven patients (4/9 oropharynx and 3/11 laryngopharynx) were grouped as aspirators (A) and remaining 13 as non-aspirators (NA). The QOL study showed that pretreatment coughing and swallowing difficulties were greater in group A versus NA and remained persistently higher. In group A, deaths attributable to aspiration were seen in 3/7 patients, while none occurred in the NA group (Fisher's exact P = 0.03). The mean PM dose was 60 Gy in both the groups and mean V60 was similar at 69 and 67% in A and NA groups, respectively. CONCLUSIONS: VFG helps identify patients who aspirate and are at risk of premature death due to its complications, alerting caregivers to direct attention appropriately.

Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas.

PURPOSE: The aim of this study was to ascertain whether diffusion tensor imaging (DTI) metrics fractional anisotropy (FA), mean diffusivity (MD), linear case (CL), planar case (CP), spherical case (CS)-can characterize a threshold dose and temporal evolution of changes in normal-appearing white matter (NAWM) of adults with low-grade gliomas (LGGs) treated with radiation therapy (RT). METHODS AND MATERIALS: Conventional and DTI imaging were performed before RT in 5 patients and subsequently, on average, at 3 months (n = 5), 8 months (n = 3), and 14 months (n = 5) following RT for a total of 18 examinations. Isodose distribution at 5-Gy intervals were visualized in all the slices of fluid attenuated inversion recovery (FLAIR) and the corresponding DTI images without diffusion sensitization (b0DTI). The latter were exported for relative quantitative analysis. RESULTS: Compared to pre-RT values, FA and CL decreased, whereas CS increased at 3 and 8 months and recovered partially at 14 months for the dose bins >55 Gy and 50-55 Gy. For the 45 50 Gy bin, the FA and CL decreased with an increase in CS at 3 months; no further change was seen at 8 or 14 months. For the >55 Gy and 50-55 Gy bins, CP decreased and MD increased at 3 months and returned to baseline at 8 months following RT. CONCLUSION: Radiation-induced changes in NAWM can be detected at 3 months after RT, with changes in FA, CL, and CS (but not CP or MD) values seen at a threshold dose of 45-50 Gy. A partial recovery was evident by 14 months to regions that received doses of 50-55 Gy and >55 Gy, thus providing an objective measure of radiation effect on NAWM.

A randomised trial of radiotherapy compared with cisplatin chemo-radiotherapy in patients with unresectable squamous cell cancer of the esophagus.

BACKGROUND AND PURPOSE: Following our phase II experience, a randomised trial was undertaken to evaluate the efficacy of adding chemotherapy to radiotherapy in patients with unresectable squamous cell cancer of the esophagus. PATIENTS AND METHODS: Patients randomised to the RT group received 50 Gy/25 fx/5 weeks of teletherapy followed 1-2 weeks later with 12 Gy/2 fx of high-dose-rate intra-lumenal brachytherapy spaced a week apart. Following the first 3 years of recruitment, due to unexpected late morbidity, brachytherapy was excluded and the protocol modified to 66 Gy/33 fx/6.5 weeks. The CRT group received identical radiotherapy with concurrent weekly cisplatin at 35 mg/m(2) for 6-7 cycles. RESULTS: Between April 1999 and December 2005, 125 patients were randomised to a RT (n=60) or CRT group (n=65). Radiotherapy treatment was completed in 78% (47/60) of the RT group and 89% (58/65) of the CRT group (P=0.10). Six or more cycles of cisplatin could be delivered in 63% (41/65), which resulted in RTOG grade 3 neutropenia of 3%. Late morbidity in the form of ulcers (5% vs. 15% odds ratio 0.29, 95% CI 0.08-1.11, P=0.08) and strictures (13% vs. 28%, odds ratio 0.40, 95% CI 0.16-1.01, P=0.05) was observed in the RT and CRT groups, respectively. At a median follow up of 23 months of all patients alive (range 6-82 months) and with 95/125 events, the median, 1, 2 and 5 year projected survival was 7.1 months, 32.3%, 22.8% and 13.7% vs. 13.4 months, 57.6%, 38.9% and 24.8% for the RT and CRT groups, respectively (hazard ratio 0.65, 95% CI 0.44-0.98, P=0.038). CONCLUSIONS: The addition of concurrent cisplatin to radiotherapy resulted in a modest improvement in survival and was associated with manageable additional acute and late morbidity.

Comparative assessment of doses to tumor, rectum, and bladder as evaluated by orthogonal radiographs vs. computer enhanced computed tomography-based intracavitary brachytherapy in cervical cancer.

PURPOSE: To carry out a comparative assessment of intracavitary brachytherapy (ICBT) doses to tumor, bladder, and rectum based on orthogonal films and contrast enhanced computed tomography (CECT). METHODS AND MATERIALS: Fifty-five ICBT procedures with CT/MRI compatible applicator and CECT scans were evaluated. Doses to Point A, International Commission on Radiation Units and Measurement (ICRU) reference points for maximum bladder (B max(ICRU)) and rectum (R max(ICRU)) localized from orthogonal films were compared with CECT delineated tumor, bladder (B max(CECT)), and rectum (R max(CECT)) doses, respectively. The 95th and 90th percentile bladder (B 95(CECT) and B 90(CECT)) and rectal (R 95(CECT) and R 90(CECT)) doses based on CECT were also estimated. RESULTS: Mean percentage tumor volume encompassed within the prescribed dose of 600 cGy to Point A was 88.8%. Mean B max(ICRU), B max(CECT), R max(ICRU), and R max(CECT) were 631.3 cGy, 1221.4 cGy, 454.8 cGy, and 526.9 cGy, respectively. Paired mean differences were significant between B max(ICRU) and B max(CECT) or B 95(CECT) (both p < 0.001); R max(ICRU) and R max(CECT) (p = 0.005) or R 90(CECT) (p < 0.001), whereas insignificant for B max(ICRU) and B 90(CECT) (p = 0.281), and R max(ICRU) and R 95(CECT) (p = 0.372). CONCLUSIONS: Prescription based on Point A ICBT doses could lead to uncertainty and underdosage in tumor. ICRU 38 maximum bladder and rectal doses significantly underestimate the maximum doses to these organs and represent the 90th and 95th percentile of the maximum doses to these organs, respectively.