Radiotherapy and palliative care outpatient clinic: a new healthcare integrated model in Italy.

BACKGROUND: On the basis of substantial evidence demonstrate that palliative care combined with standard care improves patient, caregiver, and society outcomes, we have developed a new healthcare model called radiotherapy and palliative care (RaP) outpatient clinic were a radiation oncologist and a palliative care physician make a joint evaluation of advanced cancer patients. METHODS: We performed a monocentric observational cohort study on advanced cancer patients referred for evaluation at the RaP outpatient clinic. Measures of quality of care were carried out. RESULTS: Between April 2016 and April 2018, 287 joint evaluations were performed and 260 patients were evaluated. The primary tumor was lung in 31.9% of cases. One hundred fifty (52.3%) evaluations resulted in an indication for palliative radiotherapy treatment. In 57.6% of cases was used a single dose fraction of radiotherapy (8 Gy). All the irradiated cohort completed the palliative radiotherapy treatment. An 8% of irradiated patients received the palliative radiotherapy treatment in the last 30 days of life. A total of 80% of RaP patients received palliative care assistance until the end of life. CONCLUSION: At the first descriptive analysis, the radiotherapy and palliative care model seem to respond to the need of multidisciplinary approach in order to obtain an improvement on quality of care for advanced cancer patients.

Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT).

Malignant Pleural Mesothelioma (MPM) is a rare malignancy with an overall poor prognosis. The standard therapeutic strategy in early-stage disease is trimodality therapy. In this publication, we report the preliminary toxicity results of the first 20 patients treated with accelerated hypofractionated radiotherapy. Between July 2017 to June 2019, 20 MPM patients were enrolled and treated with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. Only one case of G3 toxicity was reported, which was a bilateral pneumonitis that occurred two years after treatment probably due to superinfection. Median Time to Progression reached 18.2 months while one- and three-year Overall Survival rates were 85% (95% CI:60.4-94.9) and 49.5% (95% CI:26.5-68.9), respectively. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. Survival rates and Time to Progression are encouraging.

Prognostication in palliative radiotherapy-ProPaRT: Accuracy of prognostic scores.

Background: Prognostication can be used within a tailored decision-making process to achieve a more personalized approach to the care of patients with cancer. This prospective observational study evaluated the accuracy of the Palliative Prognostic score (PaP score) to predict survival in patients identified by oncologists as candidates for palliative radiotherapy (PRT). We also studied interrater variability for the clinical prediction of survival and PaP scores and assessed the accuracy of the Survival Prediction Score (SPS) and TEACHH score. Materials and methods: Consecutive patients were enrolled at first access to our Radiotherapy and Palliative Care Outpatient Clinic. The discriminating ability of the prognostic models was assessed using Harrell's C index, and the corresponding 95% confidence intervals (95% CI) were obtained by bootstrapping. Results: In total, 255 patients with metastatic cancer were evaluated, and 123 (48.2%) were selected for PRT, all of whom completed treatment without interruption. Then, 10.6% of the irradiated patients who died underwent treatment within the last 30 days of life. The PaP score showed an accuracy of 74.8 (95% CI, 69.5-80.1) for radiation oncologist (RO) and 80.7 (95% CI, 75.9-85.5) for palliative care physician (PCP) in predicting 30-day survival. The accuracy of TEACHH was 76.1 (95% CI, 70.9-81.3) and 64.7 (95% CI, 58.8-70.6) for RO and PCP, respectively, and the accuracy of SPS was 70 (95% CI, 64.4-75.6) and 72.8 (95% CI, 67.3-78.3). Conclusion: Accurate prognostication can identify candidates for low-fraction PRT during the last days of life who are more likely to complete the planned treatment without interruption.All the scores showed good discriminating capacity; the PaP had the higher accuracy, especially when used in a multidisciplinary way.

Pre-operative liver biopsy in cirrhotic patients with early hepatocellular carcinoma represents a safe and accurate diagnostic tool for tumour grading assessment.

BACKGROUND & AIMS: Knowledge of pre-operative tumour grade is crucial in the management of hepatocellular carcinoma (HCC) because it can influence recurrence and survival after surgery. The accuracy of pre-operative needle core biopsy (NCB) in tumour grading has been assessed in only a few studies with conflicting results. Our aim was to determine the long-term safety and the overall accuracy of NCB in assessing tumour grading in subjects who had undergone liver resection for a single HCC. METHODS: Eighty-one cirrhotic patients with HCC who had undergone NCB before liver resection were selected. Only patients with a single HCC and with at least a five-year-follow-up were included. Tumour grading was scored according to a modified Edmondson-Steiner classification: well/moderately (low grade) vs poorly-differentiated (high grade). RESULTS: In the 81 patients with a solitary HCC (mean size 4.1 ± 2.3cm) tumour grade was correctly identified by NCB in 74 out of 81 (91.4%) HCCs. NCB overall sensitivity and specificity were 65% and 98.1%, respectively, with a PPV of 92% and an NPV of 91%. No major complications (in particular tumour seeding) were observed. The overall survival rates at 1, 3, and 5 years were 83%, 62%, and 44%, respectively; the recurrence rate after a 5-year-follow-up was 56.2% for low grade and 82.3% for high grade tumours (p<0.007). CONCLUSIONS: Pre-operative NCB can be performed on early (<5 cm) HCC cirrhotic patients because it provides histologically useful information for HCC management with good accuracy and a low complication rate.

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report.

BACKGROUND: Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer (NSCLC). We describe the case of a patient with locally advanced node-positive NSCLC (LA-NSCLC) treated in a phase II prospective protocol with chemotherapy, accelerated hypofractionated radiotherapy (AHRT) and surgery in the pre-immunotherapy era. CASE SUMMARY: A 69-year-old male, ex-smoker (20 PY), with a Karnofsky performance status of 90, was diagnosed with locally advanced squamous cell lung carcinoma. He was staged by total body computed tomography (CT) scanning, and integrated 18F-fluorodeoxyglucose positron emission tomography/CT scan [cT4 cN3 cM0, stage IIIC according to TNM (tumor-node-metastasis) 8th edition] and received AHRT between chemotherapy cycles, in accordance with the study protocol (EudractCT registration 2008-006525-14). At the end of the study the patient underwent surgery, which was not part of the protocol, and showed a complete pathological response. CONCLUSION: This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement. Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications. We hypothesize that this radiotherapeutic approach, with its proven efficacy, could be delivered as a short course reducing treatment costs, increasing patient compliance and reducing toxicity. We are currently investigating the possibility of combining hypofractionation, chemotherapy and immunotherapy for patients with LA-NSCLC.

Role of Hyperbaric Oxygenation Plus Hypofractionated Stereotactic Radiotherapy in Recurrent High-Grade Glioma.

BACKGROUND: The presence of hypoxic cells in high-grade glioma (HGG) is one of major reasons for failure of local tumour control with radiotherapy (RT). The use of hyperbaric oxygen therapy (HBO) could help to overcome the problem of oxygen deficiency in poorly oxygenated regions of the tumour. We propose an innovative approach to improve the efficacy of hypofractionated stereotactic radiotherapy (HSRT) after HBO (HBO-RT) for the treatment of recurrent HGG (rHGG) and herein report the results of an ad interim analysis. METHODS: We enrolled a preliminary cohort of 9 adult patients (aged >18 years) with a diagnosis of rHGG. HSRT was administered in daily 5-Gy fractions for 3-5 consecutive days a week. Each fraction was delivered up to maximum of 60 minutes after HBO. RESULTS: Median follow-up from re-irradiation was 11.6 months (range: 3.2-11.6 months). The disease control rate (DCR) 3 months after HBO-RT was 55.5% (5 patients). Median progression-free survival (mPFS) for all patients was 5.2 months (95%CI: 1.34-NE), while 3-month and 6-month PFS was 55.5% (95%CI: 20.4-80.4) and 27.7% (95%CI: 4.4-59.1), respectively. Median overall survival (mOS) of HBO-RT was 10.7 months (95% CI: 7.7-NE). No acute or late neurologic toxicity >grade (G)2 was observed in 88.88% of patients. One patient developed G3 radionecrosis. CONCLUSIONS: HSRT delivered after HBO appears to be effective for the treatment of rHGG, it could represent an alternative, with low toxicity, to systemic therapies for patients who cannot or refuse to undergo such treatments. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT03411408.

Re-irradiation of recurrent glioblastoma using helical TomoTherapy with simultaneous integrated boost: preliminary considerations of treatment efficacy.

Although there is still no standard treatment for recurrent glioblastoma multiforme (rGBM), re-irradiation could be a therapeutic option. We retrospectively evaluated the efficacy and safety of re-irradiation using helical TomoTherapy (HT) with a simultaneous integrated boost (SIB) technique in patients with rGBM. 24 patients with rGBM underwent HT-SIB. A total dose of 20 Gy was prescribed to the Flair (fluid-attenuated inversion recovery) planning tumor volume (PTV) and 25 Gy to the PTV-boost (T1 MRI contrast enhanced area) in 5 daily fractions to the isodose of 67% (maximum dose within the PTV-boost was 37.5 Gy). Toxicity was evaluated by converting the 3D-dose distribution to the equivalent dose in 2 Gy fractions on a voxel-by-voxel basis. Median follow-up after re-irradiation was 27.8 months (range 1.6-88.5 months). Median progression-free survival (PFS) was 4 months (95% CI 2.0-7.9 months), while 6-month PFS was 41.7% (95% CI 22.2-60.1 months). Median overall survival following re-irradiation was 10.7 months (95% CI 7.4-16.1 months). There were no cases of re-operation due to early or late toxicity. Our preliminary results suggest that helical TomoTherapy with the proposed SIB technique is a safe and feasible treatment option for patients with rGBM, including those large disease volumes, reducing toxicity.

Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients.

AIM: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma. METHODS: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224. RESULTS: Median follow-up was 52 months (range: 3-115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38-3.34 and HR: 1.12, 95% CI: 1.07-1.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08-1.20 and HR: 1.14, 95% CI: 1.01-1.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61-3.41 and HR: 3.07, 95% CI: 1.11-8.53, respectively) compared to CG. CONCLUSION: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1-G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity.