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.

Early palliative care in newly diagnosed cancer in Ethiopia: feasibility randomised controlled trial and cost analysis.

OBJECTIVES: Globally, cancer deaths are rising. In low-and-middle-income countries, there is a gap in access to palliative care (PC). We designed a feasibility trial to study the initiation of early PC in patients with cancer in Addis Ababa, Ethiopia. METHODS: A randomised controlled trial (RCT) of standard cancer care versus standard cancer care plus in-home PC was conducted. Follow-up was at 8 and 12 weeks. Primary outcomes were: (1) feasibility, (2) patient-reported PC outcomes (African Palliative Care Association Palliative Outcome Scale (APCA POS)), and (3) costs. RESULTS: Of 95 adults randomised (mean age 49.5 years; 66% female), 27 completed 3 study visits. Of these, 89% had stage III or IV disease. Recruitment was feasible, but attrition was high. APCA POS use was feasible, with significant within-arm improvements: 24% versus 18% reduction (p<0.0002, p<0.0025) in PC versus standard care, respectively. Standard care subjects reported higher out-of-pocket payments (5810 Ethiopian birr) (ETB) and lost wages of informal caregivers (74 900 ETB), multiple times an average Ethiopian salary (3696 ETB). CONCLUSION: It is feasible to conduct an RCT of early PC for patients with cancer in Ethiopia. Retention was the biggest challenge. This study revealed opportunities to improve care, and important feasibility results to inform future, larger scale PC research in Ethiopia and beyond.

Definition of fields margins for the optimized 2D radiotherapy of prostate carcinoma.

Prostate cancer (PCa) is one of the most common malignancies in men both in western and developing countries. Radiotherapy (RT) is an important therapeutic option. New technologies (including 3D, intensity modulated RT, image-guided RT and, volumetric modulated arc therapy) have been introduced in the last few decades with progressive improvement of clinical outcomes. However, in many developing countries, the only treatment option is the traditional two-dimensional (2D) technique based on standard simulation. The guidelines for 2D field definition are still based on expert's opinions. The aim of the present study was to propose new practical guidelines for 2D fields definition based on 3D simulation in PCa. A total of 20 patients were enrolled. Computed tomography-simulation and pelvic magnetic resonance images were merged to define the prostate volumes. Clinical Target Volume (CTV) was defined using the European Organisation for Research and Treatment of Cancer guidelines in consideration of the four risk categories: Low, intermediate, and high risk with or without seminal vesicles involvement, respectively. Planning Target Volume (PTV) was defined by adding 10 mm to the CTV. For each category, two treatment plans were calculated using a cobalt source or 10 MV photons. Progressive optimization was achieved by evaluating 3D dose distribution. Finally, the optimal distances between field margins and radiological landmarks (bones and rectum with contrast medium) were defined. The results were reported in tabular form. Both field margins (PTV D98% >95%) needed to adequately irradiate all patients and to achieve a similar result in 95% of the enrolled patients are reported. Using a group of patients with PCa and based on a 3D planning analysis, we propose new practical guidelines for PCa 2D-RT based on current criteria for risk category and CTV, and PTV definition.

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 two-dimensional radiotherapy of pancreatic carcinoma: a feasibility study.

AIMS AND BACKGROUND: The aim of the study was to analyze the dose to be administered with two-dimensional involved-field palliative radiotherapy in advanced pancreatic carcinoma with respect to current dose-volume constraints (QUANTEC). METHODS AND STUDY DESIGN: The following standard regimens were evaluated: 30 Gy at 3 Gy/fraction (regimen A), 36 Gy at 2.4 Gy/fraction (regimen B), 45 Gy at 1.8 Gy/fraction (regimen C), and 50 Gy at 2 Gy /fraction (regimen D). The following constraints were considered: spinal cord Dmax <50 Gy, duodenum Dmax <55 Gy, liver Dmean <30 Gy, kidneys Dmean <15 Gy. For dose/fraction different from 1.8-2 Gy, the correction of constraints using a value of alpha/beta = 3 for late effects was considered. The calculation of dose/volume constraints was repeated for three different radiation beams: cobalt unit, 6 MV photons, and 15 MV photons. Standard field sizes were used and adapted according to the different beam types, using the parameters of our previous study. Respect of dose-volume constraints was assessed for each type of beam and treatment (dose per fractionation) in all patients. Treatments were considered acceptable in case of: 1) respect of the constraints for spinal cord and duodenum in all patients; 2) respect in >10/15 patients of constraints for kidneys and liver. Therefore, minor violations (<10%) of the constraints for these organs were accepted (in less than 5/15 patients), in consideration of the palliative aim of treatment. RESULTS: In regimen A (30 Gy, 3 Gy/fraction), evaluated constraints were respected in all patients, regardless of the type of energy. In regimen B (36 Gy, 2.4 Gy/fraction), constraints were met in all patients undergoing irradiation with 6 and 15 MV photons. However, using the cobalt unit, kidney constraint was respected only in 5 of 15 patients. In regimens C and D (45 Gy, 1.8 Gy/fraction and 50 Gy, 2 Gy/fraction, respectively), the constraint for the kidney was respected only in 2-5 patients, depending on the energy used. Furthermore, using 50 Gy, the spinal cord constraint was not respected in 2-3 patients, depending on the beam used. Therefore, only the following treatments were considered acceptable: 1) 30 Gy, 3 Gy/fraction, regardless of the energy used; 2) 36 Gy, 2.4 Gy/fraction, only for treatments performed with linear accelerator (6-15 MV). CONCLUSIONS: The clinical benefits of radiotherapy in pancreatic tumors should not be withheld from patients treated in centers only with two-dimensional technology. Prospective trials, particularly in developing countries, would be useful to evaluate the efficacy in this setting of involved-field two-dimensional treatments using the dose and fractionation defined in this analysis.