Radiotherapy for the treatment of distant nodes metastases from oligometastatic urothelial cancer: A retrospective case series.

OBJECTIVES: To investigate the efficacy of stereotactic body radiotherapy in oligometastatic urothelial carcinoma with node-only involvement. METHODS: We retrospectively collected data on the outcomes of patients who underwent stereotactic body radiotherapy for metastatic node lesions from oligometastatic urothelial carcinoma at Radiotherapy Unit of University Hospital of Parma, Parma, Italy. The investigated outcomes were lesion size, standardized uptake value, overall response rate, lesion control rate, lesion progression-free interval, progression-free survival and overall survival. RESULTS: Among seven patients included in the study, a total of 14 node metastatic lesions were treated with stereotactic body radiotherapy. The mean total dose of stereotactic body radiotherapy was 32 Gy (range 25-40 Gy). At first imaging evaluation, a mean variation of -4% (P = 0.427) in major diameter, -16% (P = 0.048) in minor diameter and -76% in standardized uptake value (P < 0.001) were documented. The overall response rate and lesion control rate were 43% and 100%, respectively. Median lesion progression-free interval, progression-free survival and overall survival were 11.4 months (95% CI 3.4-19.4), 2.9 months (95% CI 2.6-3.1) and 14.9 months (95% CI 12.3-17.5), respectively. Stereotactic body radiotherapy was effective in delaying the beginning of a systemic chemotherapy in four patients. CONCLUSIONS: The present findings generate the hypothesis of a possible role for the use of stereotactic body radiotherapy in selected patients with distant node metastases from oligometastatic urothelial carcinoma.

Radiotherapy of non-small-cell lung cancer in the era of EGFR gene mutations and EGF receptor tyrosine kinase inhibitors.

Non-small-cell lung cancer (NSCLC) occurs, approximately, in 80-85% of all cases of lung cancer. The majority of patients present locally advanced or metastatic disease when diagnosed, with poor prognosis. The discovery of activating mutations in the EGFR gene has started a new era of personalized treatment for NSCLC patients. To improve the treatment outcome in patients with unresectable NSCLC and, in particular, EGFR mutated, a combined strategy of radiotherapy and medical treatment can be undertaken. In this review we will discuss preclinical data regarding EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) and radiotherapy, available clinical trials investigating efficacy and toxicity of combined treatment (thoracic or whole brain radiotherapy and EGFR-TKIs) and, also, the role of local radiation in mutated EGFR patients who developed EGFR-TKI resistance.

Short-course preoperative radiotherapy combined with chemotherapy in resectable locally advanced rectal cancer: local control and quality of life.

PURPOSE: The authors sought to evaluate the clinical outcome after preoperative short-course radiotherapy (SC-RT) for locally advanced resectable rectal cancer in terms of local control (LC) and quality of life (QoL). MATERIALS AND METHODS: Patients with locally advanced rectal cancer enrolled between 1997 and 2008 in an observational study of preoperative SC-RT were analysed. The treatment algorithm was neo-adjuvant chemotherapy (CT) administered for four cycles, followed by preoperative SC-RT administered 1 week after chemotherapy completion, delivering 20 Gy in five fractions over 1 week. Immediately in the following week surgery was performed. The adjuvant 5-FU-based CT was planned for pathological stage UICC≥II. LC, overall survival (OS), disease-free survival (DFS), early and late complications (RTOG scale) were analysed. All patients completed the EORTC QoL (C-30 and C-38), Faecal Incontinence QoL, and International Index of Erectile Function questionnaires (IIEF). RESULTS: A total of 67 patients were analysed. Chemotherapy and radiotherapy were well tolerated. At the pathological analysis, stable disease was obtained in 24 patients (36%), reduction of disease stage in 34 patients (50.7%), and progression in nine cases (13.3%). Adjuvant chemotherapy was indicated in 21 patients. Two locoregional recurrences, both within the radiotherapy volume, were observed, resulting in a 5-year LC of 97%. The 5-year DFS was 84%, with mean time to systemic progression of 24 months. After a mean follow-up of 114 months, the 5-year OS rate was 67%. Late toxicity >grade II was observed in 9% of patients. High anterior resection (AR) patients had significantly better scores than low AR or abdomino-perineal resection (APR). A total of 89% of the patients treated with conservative surgery had regular anal sphincter function. In male patients undergoing AR or APR, erectile dysfunction was found in 47% and 75% of the cases, respectively. CONCLUSIONS: Preoperative SC-RT combined with chemotherapy for locally advanced resectable rectal cancers was well tolerated. This treatment resulted in favourable LC, OS, low rates of toxicity and satisfying QoL.

Prostate embryonal rhabdomyosarcoma in adults: Case report and review of literature.

INTRODUCTION: Prostate embryonal rhabdomyosarcoma (ERMS) is a common tumour in infants and children, with a median occurrence age of 5 years, but it is rare in adults. It is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethral obstruction, and systemic spread, commonly to the lungs, liver and bone. Several therapeutic approaches have been employed in the effort to treat prostate ERMS, but all of them have failed to gain a significant survival benefit in adult patients. CASE REPORT: We report on a case of a stage IV prostate ERMS, approached with combined-modality treatment, with the administration of 5 courses of doxorubicin, ifosfamide and 2-mercaptoethane sulfonate sodium (mesna), and, subsequent radiotherapy to the prostatic bed (60 Gy/30 fxs). The patient remained free of progression of disease for about 1 year to finally experience a systemic relapse with multiple lung metastases and pleural effusion. The patient died for metastatic disease 27 months following the initial diagnosis. CONCLUSION: While it remains questionable which therapeutic approach for prostate ERMS in adults is the most appropriate, our report demonstrates that a chemo-radiation combined treatment can control the prostate disease, reducing the symptoms and improving the quality of life of these patients, for the most part destined to die for systemic progression of disease.

ADM-Assisted Direct-to-Implant Prepectoral Breast Reconstruction in Postmastectomy Radiation Therapy Setting: Long-Term Results.

BACKGROUND: Postmastectomy radiotherapy (PMRT) on immediate breast reconstruction historically involved a marked increase in complication rate (up to 50%). Prepectoral breast reconstruction (PPBR) has shown promising early postoperative results. This study aims to evaluate PPBR long-term results in PMRT setting. MATERIALS AND METHODS: This is a retrospective monocentric analysis of 485 PPBR (439 patients) undergoing Acellular-Dermal-Matrix assisted direct-to-implant reconstruction (46 bilateral procedures) between January 2015 and December 2020 (mean FU:35.6 months). Group 1 comprised 401 PPBR not submitted to PMRT, and 84 reconstructions receiving PMRT in Group 2. Patients' characteristics, postoperative complication and revisional surgery rate were examined. PMRT characteristics and subcutaneous tissue thickness, measured in Group 2 by CT scan, were also evaluated. RESULTS: Long-term complication rate was 11.2% in Group 1 vs. 21.4% in Group 2 (P-value = .019). Capsular contracture represented the only complication associated to a statistically significant difference between the 2 groups (P-value < .001). In Group 2, only 4.8% implant loss and 8.3% severe capsular contracture rate was found. In patients who underwent PMRT, 38.9% of complications settled with no consequences, and only 4.8% of patients needed revisional surgery in the long-term FU. According to multivariate analysis, drug intake and PMRT were significantly associated with postoperative complications. In Group 2, a thinner subcutaneous tissue was linked to a higher complication risk. CONCLUSION: In our series, patients treated with PPBR who underwent PMRT, presented a low complication rate and minimal need for revisional surgery in the long-term follow-up, suggesting that this technique is feasible and safe also in PMRT context.

Ablative Radiotherapy (ART) for Locally Advanced Pancreatic Cancer (LAPC): Toward a New Paradigm?

Locally advanced pancreatic cancer (LAPC) represents a major urgency in oncology. Due to the massive involvement of the peripancreatic vessels, a curative-intent surgery is generally precluded. Historically, LAPC has been an indication for palliative systemic therapy. In recent years, with the introduction of intensive multi-agent chemotherapy regimens and aggressive surgical approaches, the survival of LAPC patients has significantly improved. In this complex and rapidly evolving scenario, the role of radiotherapy is still debated. The use of standard-dose conventional fractionated radiotherapy in LAPC has led to unsatisfactory oncological outcomes. However, technological advances in radiation therapy over recent years have definitively changed this paradigm. The use of ablative doses of radiotherapy, in association with image-guidance, respiratory organ-motion management, and adaptive protocols, has led to unprecedented results in terms of local control and survival. In this overview, principles, clinical applications, and current pitfalls of ablative radiotherapy (ART) as an emerging treatment option for LAPC are discussed.

Automatic feathering algorithm for VMAT craniospinal irradiation: A comprehensive comparison with other VMAT planning strategies.

In craniospinal irradiation, field matching is very sensitive to intrafraction positional uncertainties in cranio-caudal direction, which could lead to severe overdoses/underdoses inside the planning target volume. During the last decade, significant efforts were made to develop volumetric-modulated arc therapy strategies, which were less sensitive to setup uncertainties. In this study, a treatment planning system-integrated method, named automatic feathering (AF) algorithm, was compared against other volumetric-modulated arc therapy strategies. Three patients were retrospectively included. Five different planning techniques were compared, including overlap (O), staggered overlap (SO), gradient optimization (GO), overlap with AF algorithm turned on (O-AF), and staggered overlap with AF algorithm turned on (SO-AF). Three overlapping lengths were considered (5 cm, 7.5 cm, and 10 cm). The middle isocenter was shifted of ±1 mm, ±3 mm, and ±5 mm to simulate setup uncertainties. Plan robustness against simulated uncertainties was evaluated by calculating near maximum and near minimum dose differences between shifted and nonshifted plans (ΔD2%, ΔD98%). Dose differences among combinations of techniques and junction lengths were tested using Wilcoxon signed-rank test. Higher ΔD2% and ΔD98% were obtained using the overlap technique (ΔD2% = 15.4%, ΔD98% = 15.0%). O-AF and SO-AF provided comparable plan robustness to GO technique. Their performance improved significantly for grater overlapping length. For 10-cm overlap and 5-mm shift, GO, O-AF, and SO-AF yielded to the better plan robustness (5.7% < ΔD2% < 6.0%, 6.1% < ΔD98% < 7.6%). SO provided an intermediate plan robustness (9.8% < ΔD2% < 10.8%, 8.9% < ΔD98% < 10.3%). The addition of AF to the overlap technique significantly improves plan robustness especially if larger overlapping lengths are used. Using the AF algorithm, plans become as robust as plans optimized with more sophisticated and time-consuming approaches (like GO).

Abscopal effect after hypofractionated radiotherapy in metastatic renal cell carcinoma pretreated with pazopanib.

Background: The abscopal effect consists of distant metastases response after local treatment based on systemic immune stimulation. It is a rare event observed in many tumors, especially with radiotherapy and immunotherapy. Clinical case: We report the long-term abscopal effect in a metastatic renal cell carcinoma patient with lung metastasectomy, after hypofractionated radiotherapy on lymph node metastasis. The patient was pretreated with pazopanib, which was discontinued early owing to toxicity before radiotherapy. Methodology: Immunohistological analyses of the primary tumor and metastases were performed. Discussion: We supposed that radiotherapy, and maybe tyrosine kinase inhibitors, could act as immune-primers for abscopal effect modifying the immune tumor microenvironment. Conclusion: Future studies are needed to optimize the combination of radiotherapy with systemic therapy for better long-term tumor control in selected patients.

Treatment Outcome of metastatic lesions from renal cell carcinoma underGoing Extra-cranial stereotactic body radioTHERapy: The together retrospective study.

OBJECTIVES: stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients. METHODS: all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion. RESULTS: 57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions (<14 mm). SBRT was safe and the 1-year local disease control was 87.7%. After SBRT, 18 patients (37.5%) permanently interrupted systemic therapy. CONCLUSIONS: consistently with the previous literature, our findings support the use of SBRT in selected mRCC patients.

Palliative radiotherapy in advanced cancer patients treated with immune-checkpoint inhibitors: The PRACTICE study.

In the present study, the influence of purely palliative radiotherapy (pRT) on the outcomes of patients with advanced cancer undergoing immune checkpoint blockade was evaluated. Patients were stratified into three groups: Patients who had received pRT within 6 months prior to the initiation of immunotherapy (previous pRT); patients who received pRT during immunotherapy (concurrent pRT); and patients who did not receive RT prior to or during immunotherapy (no RT group), and these groups were compared. The median overall survival (mOS), median progression free survival (mPFS) and median time-to-treatment failure (mTTF) for the previous pRT group were significantly shorter compared with the no RT group (mOS, 3.6 vs. 12.1 months, respectively, P=0.0095; mPFS 1.8 vs. 5.4 months, respectively, P=0.0016; mTTF 1.8 vs. 5.7 months, respectively, P=0.0035). The concurrent pRT group had a longer mTTF compared with the previous pRT group and similar outcomes to the no RT group. In the previous pRT group, 26.9% of the patients experienced immune-related adverse events compared with 40.1% of patients in the no RT group. Despite the use of pRT during immunotherapy being considered safe, the results of the present study suggest that pRT has a negative effect on immune balance.

Effectiveness and safety of "real" concurrent stereotactic radiotherapy and immunotherapy in metastatic solid tumors: a systematic review.

BACKGROUND: in the setting of metastatic malignancies, the role of concurrent stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) and immune-checkpoint inhibitors (ICI) is increasing. Few data are available about effectiveness and safety of this strategy. METHODS: we used the PRISMA guidelines to perform a systematic review. We selected only articles reporting a "real" concurrent treatment, defined as SRS/SRT performed within 30 days of ICI administration. RESULTS: Despite several limits due to the heterogeneity and retrospective nature of the studies, 1-year local control for brain lesions ranged from 42 to 100% and 1-year regional brain control ranged from 31 to 83%. An interesting rate of local and distant control was reported for concurrent SBRT-ICI on extra-cranial lesions. No relevant signals about toxicity emerged. CONCLUSIONS: Based on published evidence, concurrent SRS/SRT and ICI seems to lead intriguing outcomes, without increasing toxicity. Further investigations are warranted to obtain stronger prospective evidence.

Hypo-fractionated IMRT for patients with newly diagnosed glioblastoma multiforme: a 6 year single institutional experience.

OBJECTIVES: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor. In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM. PATIENTS AND METHODS: Sixty-seven patients affected by GBM who had previously undergone surgical resection (total, subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6-12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS ≥ 60, age ≥ 18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25 Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival. RESULTS: All patients have completed the treatment protocol. Median age was 64.5 years (range 41-82 years) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy. No grade 3-4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively. CONCLUSIONS: The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.

Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7-9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. METHODS: We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. RESULTS: Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6-54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. CONCLUSION: Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient.