Short course palliative radiotherapy in advanced solid tumors: a pooled analysis (the SHARON project).

Previous trials showed the tolerability and efficacy of a palliative radiotherapy (RT) regimen (SHARON) based on the 4 fractions delivered in 2 days in different oncological settings. In order to identify possible predictors of symptomatic response, the purpose of this study is to perform a pooled analysis of previous trials. We analyzed the impact on symptomatic response of the following parameters: tumor site, histological type, performance status (ECOG), dominant symptom, and RT dose using the Chi-square test and Fisher's exact test. One-hundred-eighty patients were analyzed. Median RT dose was 20 Gy (range: 14-20 Gy). The overall response rate was 88.8% (95% CI 83.3-92.7%) while pre- and post-treatment mean VAS was 5.3 (± 7.7) and 2.2 (± 2.2), respectively (p < 0.001). The overall response rate of pain, dyspnea, bleeding, dysphagia, and other symptoms was 86.2%, 90.9%, 100%, 87.5%, and 100%, respectively. Comparing the symptomatic effect based on the analyzed parameters no significant differences were recorded. However, patients with locally advanced disease showed a higher rate of symptomatic responses than metastatic ones (97.3% vs 83.0%; p = 0.021). Finally, the complete pain response rate was more than double in patients with mild to moderate (VAS: 4-7) compared to those with severe (VAS > 7) pain (36.0% vs 14.3%; p = 0.028). This pooled analysis showed high efficacy of the SHARON regimen in the relief of several cancer-related symptoms. The markedly and significantly higher complete pain response rate, in patients with mild-moderate pain, suggests early referral to palliative RT for patients with cancer-related pain.

Dose-Volume Constraints fOr oRganS At risk In Radiotherapy (CORSAIR): An "All-in-One" Multicenter-Multidisciplinary Practical Summary.

BACKGROUND: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. MATERIAL AND METHODS: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin's lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. RESULTS: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. CONCLUSIONS: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations.

Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries.

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2-6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9-105.9), 77.7 Gy EQD2 (range, 56.9-99.1), 68.0 Gy EQD2 (range, 48.6-90.7) and 62.0 Gy EQD2 (range, 39.6-83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

Radiotherapy in palliation of thoracic tumors: a phase I-II study (SHARON project).

The main clinical goal for patients with advanced or metastatic thoracic cancer is palliation of tumor-related symptoms and improvement of quality of life. The aim of this phase I-II trial was to define the maximum tolerated dose (MTD) of a short-course of palliative radiotherapy (RT) and to evaluate its efficacy in terms of palliative response. A phase I trial was planned with escalating dose increments. Total doses ranged from 16 to 20 Gy delivered (BID) in two consecutive days. Dose limiting toxicity was defined as any acute grade ≥ 3 toxicity based on the RTOG scale. MTD was used in the phase II trial to evaluate the efficacy of this regimen using a two stage Simon's design. Fifty-four patients were enrolled. The upper dose level of 20 Gy was defined as the MTD. In patients treated with this dose, the overall palliative response rate was 96.5% (CI 0.95: 81.3-99.9%). Complete pain relief rate was 50.0%. Median survival without symptomatic progression was 3 months. The tested short course accelerated regimen was well tolerated and effective in the palliative setting of metastatic or locally advanced chest cancer. A phase III trial is ongoing to validate this RT schedule.Trial registration: NCT03465553.

Feasibility of 2D-conformal radiotherapy for pancreatic carcinoma.

The purpose of the present study was to propose an optimized 2D technique (2D-conformal) for radiotherapy (RT) of pancreatic cancer (CaP). This technique is based on double simulation which resolves the problems of radiographic image distortion. Five patients with locally advanced CaP were identified and enrolled. Treatment planning was simulated in 3 different ways: Two dimensional-standard (2D-SRT), 2D-conformal (2D-CRT), and three dimensional-conformal (3D-CRT) techniques for 10 MV LINAC. Simulation for a cobalt machine was also performed using only the 2D techniques. 2D-SRT technique was planned with fields definition based on anatomical landmarks (bone and duodenum). 3D-CRT was planned with standard virtual simulation technique, and 3D dose evaluation and optimization. 2D-CRT technique was based on manual information transfer from a diagnostic CT-scan to simulation radiograms. To eliminate the X-ray image distortion, a double simulation was employed and the profile of the GTV was delineated on radiographs bearing the simulator isocenter into the target center. Concerning target irradiation of either LINAC (10 MV) or cobalt source, the PTV constraints (ICRU 62) were met in all patients (Dmin >95%, Dmax <107%) with all techniques (2D-SRT, 3D-CRT, 2D-CRT). For organs at risk irradiation, in terms of Dmax to both duodenum and spinal cord, similar results were recorded with all techniques using the LINAC (10 MV). Liver and kidneys Dmean gradually improved from 2D-SRT to 2D-CRT and 3D-CRT. The 2D-CRT compared to 2D-SRT technique, halved the average dose to the liver and reduced to about 1/3 the average dose to the kidneys. With the cobalt source, using the 2D-CRT produced a reduction of Dmean to the kidneys (median from 30.7 to 16.9%) and liver (median from 33.4 to 22.3%) compared to 2D-SRT. This analysis showed better planning results in RT treatment of CaP while using a 2D-CRT compared to 2D-SRT technique and therefore presents an example for optimized 2D RT use.

Short-course regimen of palliative radiotherapy in complicated bone metastases: a phase i-ii study (SHARON Project).

Metastases with soft tissues invasion, impending fractures or spinal cord compression (complicated bone metastases) represent a common clinical problem in advanced cancers and frequently lead to deterioration of patients' quality of life (QoL). A phase I-II study was planned to define the maximum tolerated dose (MTD) of a short-course radiotherapy (RT) and its efficacy in palliation of complicated bone metastases. A phase I trial was designed with three dose-escalation steps: 16, 18, and 20 Gy. Total dose at each level was delivered in 2 days, twice daily. Eligibility criteria were painful complicated bone metastases and ECOG performance status ≤ 3. The presence of acute toxicity ≥ Grade 3 (RTOG scale) was considered the dose limiting toxicity. The MTD was used to plan a phase II trial with pain response as the primary outcome. Pain was recorded using a Visual Analogic Scale (VAS), and QoL using CLAS scales. Forty-five patients were enrolled in this trial. In phase I no Grade ≥ 2 acute toxicities were recorded. Thus 20 Gy was established as MTD. In phase II, with a median follow-up of 4 months, rates of complete symptom remission, partial response, no symptomatic change, and symptoms progression were 32.0%, 52.0%, 8.0%, and 8.0%, respectively. This RT protocol tested in our study is effective and tolerable with comparable results to traditional RT treatments delivered in 5-10 daily fractions.

Definition of fields margins for palliative radiotherapy of pancreatic carcinoma.

The present study aimed to provide practical guidelines for palliative treatment of advanced carcinoma of the pancreas (CAP) with the 2D technique. Fifteen patients with locally advanced CAP consecutively treated with radiation therapy at the Radiation Oncology Center, Research and Care Foundation 'Giovanni Paolo II' (Campobasso, Italy) underwent computed tomography simulation in supine position. Definition of the clinical target volume (CTV) included the head and body of the pancreas, and the retropancreatic space. The planning target volume was defined by adding a margin of 14 mm to the CTV in the cranio-caudal direction and of 11 mm in radial direction. For each patient, 3 treatment plans were calculated using a cobalt source, 6 MV photons and 15 MV photons (box technique). Beams were drawn using the primary collimators without using multileaf collimators, and progressively optimized in order to respect the minimum dose (Dmin>90%) constraint. Once the final plan was achieved, distances of the fields edges from a set of reference points (bony or duodenal landmarks) were measured. Using this technique, 15 anterior-posterior and postero-anterior (AP-PA) beams and 15 pairs of lateral-lateral (LL) beams were defined for the different patients. Finally, the single minimal AP-PA and LL beams able to include the 15 sets of AP-PA and LL beams were defined. The results of this analysis are reported in tabular form. Guidelines are provided for treatment based on cobalt unit or Linear accelerator (both 6 and 15 MV photons). This study provides information regarding field size and position. A dosimetric study has been planned to identify the dose to be administered with this technique taking into account current dose-volume constraints.

Phase I-II Study of Short-course Accelerated Radiotherapy (SHARON) for Palliation in Head and Neck Cancer.

AIM: To determine the maximum tolerated dose (MTD) of a short-course accelerated radiotherapy and its feasibility for symptomatic palliation of advanced head and neck cancer or head and neck metastases from any primary site. PATIENTS AND METHODS: A phase I trial in four dose-escalation steps was planned: total dose ranged between 14 and 20 Gy in a total of four fractions administered twice a day. The dose-limiting toxicity (DLT) was determined as grade 3 or more toxicity occurring during treatment. The MTD obtained was used to plan a phase II trial. RESULTS: A total of 48 patients were treated. In the phase I trial, the 20 Gy dose level was determined to be the MTD. In the phase II trial, the palliative response rate was 82.7%, with a median duration of palliation of 3 months. CONCLUSION: Short-course accelerated radiotherapy was well tolerated and effective for palliation. These findings may help design future prospective randomized studies.

Short course accelerated radiation therapy (SHARON) in palliative treatment of advanced solid cancer in older patients: A pooled analysis.

OBJECTIVES: To evaluate the efficacy and safety of a conformal Short Course Accelerated Radiation therapy (SHARON) for symptomatic palliation of locally advanced or metastatic cancers in older patients. MATERIALS AND METHODS: This is a pooled analysis on patients aged ≥80 years selected between subjects enrolled in 3 phase I-II studies on a short course palliative treatment of advanced or metastatic cancer. The primary endpoint was to evaluate the symptoms response rate produced by accelerated radiotherapy delivered in 4 total fractions in twice a day. Total dose ranged between 14 Gy and 20 Gy while dose/fraction between 3.5 and 5 Gy. RESULTS: A total of 48 patients were included in this analysis. Twenty-six patients (54.2%) had advanced primary or metastatic head and neck tumors, 11 (22.9%) locally advanced or metastatic thoracic cancers, 11 (22.9%) complicated bone metastases. The majority of patients presented pain (60.4%). With a median follow-up time of 5.5 months, no G4 acute and late toxicities were recorded. The overall palliative response rate was 91.7% with a median duration of palliation of 4 months. CONCLUSION: Short course accelerated radiotherapy in locally advanced or metastatic cancers is effective in terms of symptom relief and well tolerated even in older patients.

Palliative Short-Course Radiation Therapy in Rectal Cancer: A Phase 2 Study.

PURPOSE: The management of patients with symptomatic rectal cancer not amenable to curative treatment may be challenging. The aim of this phase 2 study was to evaluate the efficacy of short-course radiation therapy in patients with obstructing rectal cancer. METHODS AND MATERIALS: Patients who were not candidates for surgical resection because of synchronous metastases, age, and/or comorbidities were considered eligible. The sample size was calculated based on the 2-stage design of Simon. Short-course radiation therapy was delivered with an isocentric 4-field box technique (total, 25 Gy; 5 fractions in 5 days). Chemotherapy was suspended during radiation treatment. Clinical outcome measures were symptomatic response rate, toxicity, colostomy-free survival, and overall survival. RESULTS: From October 2003 to November 2012, 18 patients (median age, 77.5 years) were enrolled. The median follow-up was 11.5 months (range, 3-36 months). Four weeks after treatment, a complete response (ie, complete symptom resolution) was observed in 38.9% of patients and a partial response in 50.0% cases, whereas 11.1% had no response. The rates of reduction or resolution of pain and bleeding were 87.5% and 100%, respectively. The 1-, 2-, and 3-year colostomy-free survival rates were 100%, 71.4%, and 47.6%, respectively (median, 30 months). The 1-, 2-, and 3-year cumulative overall survival rates were 85.2%, 53%, and 39.8%, respectively (median, 25 months). No patients stopped treatment because of gastrointestinal or genitourinary toxicities: 38.9% of patients had grade 1 to 2 toxicity, and 16.7% had grade 3 toxicity. Only 1 patient had hematologic grade 2 toxicity, and 2 patients had grade 2 skin toxicity. CONCLUSIONS: Short-course radiation therapy may represent a safe and effective alternative treatment option in patients with obstructing rectal cancer not eligible for curative treatment, allowing colostomy to be avoided in a substantial proportion of patients.

Cancer care scenario in Bangladesh.

Bangladesh is a developing country that is facing many challenges, especially in the health sector. Cancer management is a priority due to the current trend of increased incidence in this region. In this article, the current scenario of cancer in Bangladesh and its management with brief history is outlined. The combined effort of government and private sector is highlighted with the gradual progress in cancer management. Recent introduction of the state-of-the-art facilities and the training facilities for human resource development are also outlined. The existing challenges and cooperation from local NGOs and other overseas sources are also highlighted to provide an insight regarding possible ways to tackle these challenges to ensure a better future.