18F-fluorodeoxyglucose PET-CT-guided pelvic chemoradiation therapy using helical tomotherapy for locally advanced carcinoma cervix without para-aortic nodal disease: Clinical and patient-reported outcomes from a prospective phase 2 study.

INTRODUCTION: Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic information from 18 fluro-deoxyglucose positron emission tomography combined with contrast-enhanced computerized tomography (FDG PET-CT) may potentially augment treatment decision-making for LACC. This study ascertained FDG-PET CT influence on chemoradiation therapy (CTRT) decisions in LACC. We report oncologic and patient-reported outcome measures (PROMs). METHODS: FDG PET-CT scans were reviewed independently by two nuclear medicine specialists and two radiation oncologists. Pelvic CTRT plan digressions were documented and therapy was adapted accordingly. Pelvis radiation (50 Gy/25#/5 weeks) using tomotherapy with weekly cisplatin was used in node-negative disease. Dose-escalated simultaneous integrated boost (SIB) 60 Gy/25#/5 weeks was delivered to involved pelvic nodes. All received brachytherapy. Post-treatment PET-CT scans were at 6 months. Functional assessment of cancer therapy scores were calculated at baseline, treatment completion, 3 months, 1 year and 3 years. RESULTS: Between November 2015 and January 2018, 85 patients were screened, and 77 consented. Extrapelvic disease was seen in 12 (16%) patients (9 para-aortic nodes, 2 distant metastases and 1 synchronous carcinoma breast); 60 patients were included in the final analysis. Decision changes were seen in 10/77 (13%) screened, 8/60 (13%) included and 32 (53.3%) received SIB. Post-treatment, 27 (45%) had grade 2 GI/GU/GYN toxicity, one (2%) had grade 3 GI and five (8.3%) had grade 3 neutropenia. At median overall survival of 54.2 months (95% CI 52.8-58.3), 5-year local failure, pelvic nodal and para-aortic nodal-free survival were 86.8% (95% CI 78.0-96.6), 85.2% (95% CI 76.1-95.3) and 85.2% (95% CI 76.2-95.4). Functional assessment of cancer therapy trial outcome index (FACT TOI) improved by 10.43 at 3 months with no further decline. Grade 3 toxicity was noted for abdominal pain in one (1.7%), cystitis in four (6.7%) and lymphoedema in one (1.7%) at 5 years. CONCLUSION: PET-CT resulted in major decision changes in 13%. PET-adapted CTRT was associated with acceptable toxicity, encouraging long-term survival and improvement in PROMS.

Alleviating Morbidity From Locally Advanced Breast Cancer Using a Practical and Short Radiation Therapy Regimen: Results of the HYPORT Palliative Studies.

PURPOSE: Locally advanced breast cancers lead to debilitating local symptoms. Treatment of these women encountered commonly in less resourced countries is not backed by strong evidence. We formulated the  HYPORT and HYPORT B phase 1/2 studies to evaluate the safety and efficacy of hypofractionated palliative breast radiation therapy. METHODS AND MATERIALS: Two studies (35 Gy/10 fractions; HYPORT ) and (26 Gy to breast/32 Gy tumor boost in 5 fractions; HYPORT B) were designed with increasing hypofractionation to save overall treatment time from 10 to 5 days. We report the acute toxicity, symptomatic, metabolic response, and quality of life (QOL) changes after radiation therapy. RESULTS: Fifty-eight patients, the majority of whom were pretreated with systemic therapy, completed the treatment. No grade 3 toxicity was reported. Response assessment at 3 months showed improvement in ulceration (58% vs 22%, P = .013) and bleeding (22% vs 0%, P = .074) within the HYPORT study. Similarly, in the HYPORT B study, ulceration (64% and 39%, P = .2), fungating (26% and 0%, P = .041), bleeding (26% and 4.3%, P = .074), and discharge (57% and 8.7%, P = .003) was reduced. Metabolic response was noted in 90% and 83% of patients, respectively, in the 2 studies. Improvement in the QOL scores were evident in both studies. Only 10% of the patients relapsed locally within 1 year. CONCLUSIONS: Palliative ultrahypofractionated radiation therapy to the breast is well tolerated, is effective, and results in a durable response with improved QOL. This could be considered a standard for locoregional symptom control.

Prioritizing Delivery of Cancer Treatment During a COVID-19 Lockdown: The Experience of a Clinical Oncology Service in India.

PURPOSE: A COVID-19 lockdown in India posed significant challenges to the continuation of radiotherapy (RT) and systemic therapy services. Although several COVID-19 service guidelines have been promulgated, implementation data are yet unavailable. We performed a comprehensive audit of the implementation of services in a clinical oncology department. METHODS: A departmental protocol of priority-based treatment guidance was developed, and a departmental staff rotation policy was implemented. Data were collected for the period of lockdown on outpatient visits, starting, and delivery of RT and systemic therapy. Adherence to protocol was audited, and factors affecting change from pre-COVID standards analyzed by multivariate logistic regression. RESULTS: Outpatient consults dropped by 58%. Planned RT starts were implemented in 90%, 100%, 92%, 90%, and 75% of priority level 1-5 patients. Although 17% had a deferred start, the median time to start of adjuvant RT and overall treatment times were maintained. Concurrent chemotherapy was administered in 89% of those eligible. Systemic therapy was administered to 84.5% of planned patients. However, 33% and 57% of curative and palliative patients had modifications in cycle duration or deferrals. The patient's inability to come was the most common reason for RT or ST deviation. Factors independently associated with a change from pre-COVID practice was priority-level allocation for RT and age and palliative intent for systemic therapy. CONCLUSION: Despite significant access limitations, a planned priority-based system of delivery of treatment could be implemented.

Development and validation of a decision support tool to select IMRT as radiotherapy treatment planning modality for patients with locoregionally advanced non-small cell lung cancers (NSCLC).

OBJECTIVE:: Radiation planning for locally-advanced non-small cell lung cancer (NSCLC) can be time-consuming and iterative. Many cases cannot be planned satisfactorily using multisegment three-dimensional conformal radiotherapy (3DCRT). We sought to develop and validate a predictive model which could estimate the probability that acceptable target volume coverage would need intensity modulated radiotherapy (IMRT). METHODS:: Variables related to the planning target volume (PTV) and topography were identified heuristically. These included the PTV, it's craniocaudal extent, the ratio of PTV to total lung volume, distance of the centroid of the PTV from the spinal canal, and the extent PTV crossed the midline. Metrics were chosen such that they could be measured objectively, quickly and reproducibly. A logistic regression model was trained and validated on 202 patients with NSCLC. A group of patients who had both complex 3DCRT and IMRT planned was then used to derive the utility of the use of such a model in the clinic based on the time taken for planning such complex 3DCRT. RESULTS:: Of the 202 patients, 93 received IMRT, as they had larger volumes crossing midline. The final model showed a good rank discrimination (Harrell's C-index 0.84) and low calibration error (mean absolute error of 0.014). Predictive accuracy in an external dataset was 92%. The final model was presented as a nomogram. Using this model, the dosimetrist can save a median planning time of 168 min per case. CONCLUSION:: We developed and validated a data-driven, decision aid which can reproducibly determine the best planning technique for locally-advanced NSCLC. ADVANCES IN KNOWLEDGE:: Our validated, data-driven decision aid can help the planner to determine the need for IMRT in locally advanced NSCLC saving significant planning time in the process.

Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiation therapy for left sided breast cancer patients: A prospective service development analysis.

INTRODUCTION: Use of deep inspiration breath hold (DIBH) radiation therapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements, and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers. METHODS AND MATERIALS: Data regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiation therapy were compiled prospectively for all personnel (regarding person-hours [PH]). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared with the DIBH plan. Mortality reduction from use of DIBH was calculated using the years of life lost resulting from ischemic heart disease for Indians and the postulated reduction in risk of major cardiac events resulting from reduced cardiac dose. RESULTS: The median reduction in mean heart dose between the DIBH and FB plans was 166.7 cGy (interquartile range, 62.7-257.4). An extra 6.76 PH were required when implementing DIBH as compared with FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess years of life lost from ischemic heart disease if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8 hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left-sided breast cancers at 2.3 times the annual per capita gross domestic product. CONCLUSION: Although routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.

Radical radiotherapy or chemoradiotherapy for inoperable, locally advanced, non-small cell lung cancer: Analysis of patient profile, treatment approaches, and outcomes for 213 patients at a tertiary cancer center.

INTRODUCTION: Radical radiotherapy (RT) with curative intent, with or without chemotherapy, is the standard treatment for inoperable, locally advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively reviewed the data for all 288 patients who presented with inoperable, locally advanced NSCLC at our institution, between May 2011 and December 2016. RESULTS: RT alone or sequential chemoradiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT) was used for 213 patients. Median age was 64 years (range: 27-88 years). Stage-III was the biggest stage group with 189 (88.7%) patients. Most patients with performance status (PS) 0 or 1 received CCRT, whereas most patients with PS 2 received RT alone (P < 0.001). CCRT, SCRT, and RT alone were used for 120 (56.3%), 24 (11.3%), and 69 (32.4%) patients, respectively. A third of all patients (32.4%) required either volumetric-modulated arc radiotherapy (VMAT) or tomotherapy. Median follow-up was 16 months. The median progression-free survival and median overall survival (OS) were 11 and 20 months, respectively. One-year OS and 2-year OS were 67.9% and 40.7%, respectively. Patients treated using CCRT lived significantly longer with a median survival of 28 months, compared with 13 months using SCRT and RT alone (P < 0.001). On multivariate analysis, OS was significantly affected by age, stage group, treatment approach, and response to treatment. CONCLUSION: RT including CCRT is feasible, safe, and well tolerated in our patient population and results in survival benefits comparable with published literature. CCRT should be considered for all patients with inoperable, locally advanced NSCLC, who are fit and have good PS.

Hypofractionated radiotherapy for breast cancers--preliminary results from a tertiary care center in eastern India.

BACKGROUND: The standard radiotherapy (RT) fractionation practiced in India and worldwide is 50 Gy in 25 fractions over 5 weeks to the chest wall or whole breast followed by tumour bed boost in case of breast conservation (BCS). A body of validated data exists regarding hypofractionation in breast cancer. We here report initial results for 135 patients treated at our center with the START-B type of fractionation. MATERIALS AND METHODS: From May 2011 till July 2012, women with all stages of breast cancer (excluding metastatic), who had undergone BCS or mastectomy were planned for 40 Gy in 15 fractions over 3 weeks to chest wall/whole breast and supraclavicular fossa (where indicated) followed by tumour bed boost in BCS patients. Planning was done using Casebow's technique. The primary end point was to assess the acute toxicity and the cosmetic outcomes. Using cosmetic scales; patients were assessed during radiotherapy and at subsequent follow up visits with the radiation oncologist. RESULTS: Of the 135 patients, 62 had undergone BCS and 73 mastectomy. Median age of the population was 52 years. Some 80% were T1 and T2 tumours in BCS whereas most patients in mastectomy group were T3 and T4 tumours (60%). 45% were node negative in BCS group whilst it was 23% in the mastectomy group. Average NPI scores were 3.9 and 4.9, respectively. Most frequently reported histopathology report was infiltrating ductal carcinoma (87%), grade III being most common (58%), and 69% were ER positive tumours, and 30% were Her 2 Neu positive. Triple negative tumours accounted for 13% and their mean age was young (43 yrs.) The maximum acute skin toxicity at the end of treatment was Grade 1 in 94% of the mastectomy group patients and 71% in BCS patients. Grade 2 toxicity was 6% in mast group and 23% in BCS group. Grade 3 was 6% in BCS group, no grade 3 toxicity in mastectomy patients and there was no grade 4 skin toxicity in any case. Post RT at 1 month; 39% of BCS patients had persisting Grade I skin reaction which was only 2% in mastectomy patients. At 3 months post RT, 18% patients had persisting hyperpigmentation. At 6 months 8% patients had persisting erythema in the BCS group only. Some 3% BCS and 8% mastectomy patients had lymph edema till the date of evaluation. Cosmetic outcome in BCS patients remained good to excellent 6 months post surgery and radiotherapy. 1 patient of BCS and 3 patients of mast had developed metastatic disease at the time of evaluation. CONCLUSIONS: Hypofractionated RT is well tolerated in Indian population with reduced acute skin toxicity and good cosmetic outcome. Regimens such as these should be encouraged in other centers to increase machine output time. The study is on-going to assess long term results.