Belal Ahmad

Inter-observer and intra-observer reliability for lung cancer target volume delineation in the 4D-CT era

BACKGROUND AND PURPOSEnTo investigate inter-observer and intra-observer target volume delineation (TVD) error in 4D-CT imaging of thoracic tumours.nnnMATERIALS AND METHODSnPrimary and nodal gross tumour volumes (GTV) of 10 lung tumours on the 10 respiratory phases of a 4D-CT scan were contoured by six radiation oncologist observers. Inter-observer and intra-observer variability were assessed by the coefficient of variation (COV) and the volume overlap index (VOI). ANOVA was performed to assess differences in inter-observer and intra-observer variability based on patient case difficulty, respiratory phase, physician seniority, and physician observer.nnnRESULTSnVOI analysis determined that inter-observer was a more significant source of error than intra-observer variability. VOI improved with the use of 4D-CT as compared to conventional CT. ANOVA analysis for COVs found case difficulty (easy versus difficult) to be significant for inter-observer primary tumour and intra-observer nodal disease delineation. Physician seniority, respiratory phase, and individual physician were not found to be significant for TVD error.nnnCONCLUSIONnVariability in TVD is a major source of error in 4D-CT treatment planning. Development of measures to reduce inter-observer and intra-observer TVD variability are necessary in order to deliver high quality radiotherapy.

A Phase II Trial of Arc-Based Hypofractionated Intensity-Modulated Radiotherapy in Localized Prostate Cancer

PURPOSEnTo evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and biochemical control of hypofractionated, image-guided (fiducial markers or ultrasound guidance), simplified intensity-modulated arc therapy for localized prostate cancer.nnnMETHODS AND MATERIALSnThis Phase II prospective clinical trial for T1a-2cNXM0 prostate cancer enrolled 66 patients who received 63.2 Gy in 20 fractions over 4 weeks. Fiducial markers were used for image guidance in 30 patients and daily ultrasound for the remainder. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.nnnRESULTSnMedian follow-up was 36 months. Acute Phase Grade 2 and 3 toxicity was 34% and 9% for GU vs. 25% and 10% for GI symptoms. One Grade 4 acute GI toxicity occurred in a patient with unrecognized Crohns disease. Late Grade 2 and 3 toxicity for GU was 14% and 5%, and GI toxicity was 25% and 3%. One late GI Grade 4 toxicity was observed in a patient with significant comorbidities (anticoagulation, vascular disease). Acute GI toxicity ≥ Grade 2 was shown to be a predictor for late toxicity Grade ≥ 2 (p < 0.001). The biochemical disease-free survival at 3 years was 95%.nnnCONCLUSIONSnHypofractionated simplified intensity-modulated arc therapy radiotherapy given as 63.2 Gy in 20 fractions demonstrated promising biochemical control rates; however, higher rates of acute Grade 3 GU and GI toxicity and higher late Grade 2 GU and GI toxicity were noted. Ongoing randomized controlled trials should ultimately clarify issues regarding patient selection and the true rate of severe toxicity that can be directly attributed to hypofractionated radiotherapy.

Technology Assessment of Automated Atlas Based Segmentation in Prostate Bed Contouring

BackgroundProstate bed (PB) contouring is time consuming and associated with inter-observer variability. We evaluated an automated atlas-based segmentation (AABS) engine in its potential to reduce contouring time and inter-observer variability.MethodsAn atlas builder (AB) manually contoured the prostate bed, rectum, left femoral head (LFH), right femoral head (RFH), bladder, and penile bulb of 75 post-prostatectomy cases to create an atlas according to the recent RTOG guidelines. 5 other Radiation Oncologists (RO) and the AABS contoured 5 new cases. A STAPLE contour for each of the 5 patients was generated. All contours were anonymized and sent back to the 5 RO to be edited as clinically necessary. All contouring times were recorded. The dice similarity coefficient (DSC) was used to evaluate the unedited- and edited- AABS and inter-observer variability among the RO. Descriptive statistics, paired t-tests and a Pearson correlation were performed. ANOVA analysis using logit transformations of DSC values was calculated to assess inter-observer variability.ResultsThe mean time for manual contours and AABS was 17.5- and 14.1 minutes respectively (p = 0.003). The DSC results (mean, SD) for the comparison of the unedited-AABS versus STAPLE contours for the PB (0.48, 0.17), bladder (0.67, 0.19), LFH (0.92, 0.01), RFH (0.92, 0.01), penile bulb (0.33, 0.25) and rectum (0.59, 0.11). The DSC results (mean, SD) for the comparison of the edited-AABS versus STAPLE contours for the PB (0.67, 0.19), bladder (0.88, 0.13), LFH (0.93, 0.01), RFH (0.92, 0.01), penile bulb (0.54, 0.21) and rectum (0.78, 0.12). The DSC results (mean, SD) for the comparison of the edited-AABS versus the expert panel for the PB (0.47, 0.16), bladder (0.67, 0.18), LFH (0.83, 0.18), RFH (0.83, 0.17), penile bulb (0.31, 0.23) and rectum (0.58, 0.09). The DSC results (mean, SD) for the comparison of the STAPLE contours and the 5 RO are PB (0.78, 0.15), bladder (0.96, 0.02), left femoral head (0.87, 0.19), right femoral head (0.87, 0.19), penile bulb (0.70, 0.17) and the rectum (0.89, 0.06). The ANOVA analysis suggests inter-observer variability among at least one of the 5 RO (p value = 0.002).ConclusionThe AABS tool results in a time savings, and when used to generate auto-contours for the femoral heads, bladder and rectum had superior to good spatial overlap. However, the generated auto-contours for the prostate bed and penile bulb need improvement.

Stereotactic Ablative Radiotherapy (SABR) for Large Renal Tumors: A Retrospective Case Series Evaluating Clinical Outcomes, Toxicity, and Technical Considerations.

Objectives: Metastatic renal cell carcinoma represents a clinical scenario where aggressive treatment to the primary tumor (ie, cytoreductive nephrectomy) is associated with a survival benefit. We hypothesized that stereotactic ablative radiotherapy (SABR) could be a safe alternative local modality for inoperable metastatic renal cell carcinoma patients. Our study objectives were to report on technical considerations, toxicity, and clinical outcomes of our institutional experience with renal SABR. Materials and Methods: Patients who underwent renal SABR at our institution between January 2008 and June 2015 were reviewed. Toxicity was quantified using the Common Terminology Criteria for Adverse Events version 4.0. Radiographic response was evaluated using the Response Evaluation Criteria in Solid Tumors classification. Median overall survival and follow-up were calculated using the Kaplan-Meier and reverse Kaplan-Meier methods, respectively. Results: We identified 11 patients that met study criteria. SABR was directed to the tumor or whole kidney in 5 fractions to a dose of 25 to 40 Gy. Median tumor diameter and planning target volume were 9.5 cm (range, 7.5 to 24.4) and 819.3 cm3 (range, 313.4 to 5704.3), respectively. Median follow-up was 3.9 years (95% confidence interval, 0.6-4.9). Five cases of grade 1 toxicity were reported. In the patient with the largest target, grade 2 diarrhea and probable grade 3 nausea were observed. In patients with available follow-up imaging (7/11), stable disease (n=5), partial response (n=1), and progressive disease (n=1) were observed. Median overall survival was 20.4 months (95% confidence interval, 2.30-N/A). Conclusions: In this small cohort, renal SABR was delivered with minimal toxicity. A prospective study is underway at our institution to determine maximum tolerable and optimal dosing (NCT02264548).

Evaluation of tomotherapy MVCT image enhancement program for tumor volume delineation

The aims of this study were to investigate the variability between physicians in delineation of head and neck tumors on original tomotherapy megavoltage CT (MVCT) studies and corresponding software enhanced MVCT images, and to establish an optimal approach for evaluation of image improvement. Five physicians contoured the gross tumor volume (GTV) for three head and neck cancer patients on 34 original and enhanced MVCT studies. Variation between original and enhanced MVCT studies was quantified by DICE coefficient and the coefficient of variance. Based on volume of agreement between physicians, higher correlation in terms of average DICE coefficients was observed in GTV delineation for enhanced MVCT for patients 1, 2, and 3 by 15%, 3%, and 7%, respectively, while delineation variance among physicians was reduced using enhanced MVCT for 12 of 17 weekly image studies. Enhanced MVCT provides advantages in reduction of variance among physicians in delineation of the GTV. Agreement on contouring by the same physician on both original and enhanced MVCT was equally high. PACS numbers: 87.57.N‐, 87.57.np, 87.57.nt

A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma

BackgroundCytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). As many patients are ineligible for major surgery, we hypothesized that SABR could be a safe alternative.MethodsIn this dose-escalation trial, inoperable mRCC patients underwent SABR targeting the entire affected kidney. Toxicity (CTCAE v3.0), quality of life (QoL), renal function, and tumour response (RECIST v1.0) were assessed.ResultsTwelve patients of mostly intermediate (67%) or poor (25%) International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class, median KPS of 70%, and median tumour size of 8.7xa0cm (range: 4.8–13.8) were enrolled in successive dose cohorts of 25 (nxa0=u20093), 30 (nxa0=u20096), and 35xa0Gy (nu2009=u20093) in 5 fractions. SABR was well tolerated with 3 grade 3 events: fatigue (2) and bone pain (1). QoL decreased for physical well-being (pxa0=u20090.016), but remained unchanged in other domains. SABR achieved a median tumour size reduction of −u200917.3% (range: +u20095.3 to −u200954.4) at 5.3xa0months. All patients progressed systemically and median OS was 6.7xa0months. Crude median follow-up was 5.8xa0months.ConclusionsIn non-operable mRCC patients, renal-ablative SABR to 35xa0Gy in 5 fractions yielded acceptable toxicity, renal function preservation, and stable QoL. SABR merits further prospective investigation as an alternative to cytoreductive nephrectomy.Trial RegistrationClinicalTrials.gov NCT02264548. Registered July 22 2014 – Retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT02264548

Assessment of function and quality of life in a phase II multi-institutional clinical trial of fractionated simultaneous in-field boost radiotherapy for patients with 1–3 metastases

Abstract We examined functional outcomesxa0and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1–3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30xa0Gy/10)xa0+xa0simultaneous FSRT, (60xa0Gy/10). Median overall follow-up and survival was 5.4xa0months, 6xa0month actuarial intra-lesional control was 78xa0%; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min–Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70–100), 28 (21–30) and 143 (98–153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall toxa0<27) ranged from 26 to 38xa0% for KPS, 32–59xa0% for FACT-Br and 0–16xa0% for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (≤6xa0months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6xa0weeks to 3xa0months) with no significant change in MMSE. The effects on function and quality of life of this integrated treatment of WBRTxa0+xa0simultaneous FSRT were similar to other published series combining WBRTxa0+xa0radiosurgery.