The impact of patient preference in the treatment algorithm for recurrent/metastatic head and neck squamous cell carcinoma.

The advent of immune checkpoint inhibitors for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) has revolutionized the standard of care approach in first-line treatment. The heterogeneity of disease presentation and treatment-related toxicities can be associated with suboptimal patient compliance to oncologic care. Hence, prioritizing quality of life and well-being are crucial aspects to be considered in tailoring the best treatment choice. The aim of our work is to present a short report on the topic of the patient's preference in regard to treatment and its consequences on quality of life in the recurrent/metastatic setting. According to the literature, there's an unmet need on how to assess patient attitude in respect to the choice of treatment. In view of the availability of different therapeutic strategies in first-line management of RM-HNSCC, increasing emphasis should be put on integrating patient preferences into the medical decision-making.

A narrative review of postoperative adjuvant radiotherapy for non-small cell lung cancer.

Objective: To summarize the principal studies investigating the role of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) and to discuss the recent major breakthroughs deriving from the Lung ART trial, in order to provide a real-world scenario of the management of resected NSCLC patients. Background: Surgery followed by platinum-based chemotherapy remains the mainstay of adjuvant treatments for completely resected stage II and IIIA NSCLC. Less consistent is the employment of PORT, as no significant benefit was clearly identified from the previous published meta-analysis. Furthermore, the recent results of Lung ART trial questioned for the first time the efficacy of PORT for pathological N2 (pN2) NSCLC patients. Hence, the need to define if PORT still has a role for resected NSCLC and which subgroup of patients could benefit most from this treatment. Methods: A literature search of PubMed was performed to identify publications, including prospective and retrospective clinical studies, meta-analysis and systematic review of PORT for NSCLC. No limit concerning years of publication or publication status were applied. Only papers using the English language were selected. The ESMO 2020 and ESMO 2021 online resources were used to analyze the Lung ART trial results. The authors provide a narrative summary of the findings and implications of these studies and how they improve the clinical practice. Conclusions: PORT was considered the standard of care for patients with completely resected pN2 NSCLC based on the results of an old meta-analysis that did not demonstrate a detrimental effect. The more recent randomized phase III Lung ART trial concluded that PORT could not anymore be recommended for pN2 NSCLC as a significant benefit in terms of 3 years disease-free survival (DFS) was not reached and an increased rate of radiotherapy related toxicity was observed. Retrospective studies suggest a possible role of PORT for incompletely resected NSCLC patients and those with an extranodal extension (ENE), but this issue needs to be reinforced from randomized prospective trials. The extensive publication of Lung ART trial is largely awaited to define if there is a role of PORT for resected NSCLC patients.

Dose-escalated pelvic radiotherapy for prostate cancer in definitive or postoperative setting.

PURPOSE: Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario. METHODS: Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes ≤ / > 60 Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored. RESULTS: ISUP pattern < 2 was a significant predictor of improved b-RFS (HR = 0.3, 95% CI 0.1220-0.7647, P = 0.0113), while total dose < 60 Gy to positive pelvic nodes was associated with worse b-RFS (HR = 3.59, 95% CI 1.3245-9.741, P = 0.01). Conversely, treatment setting (postoperative vs definitive) and treatment delivery technique (SIB vs sequential boost) were not associated with significant differences in terms of b-RFS (HR = 0.85, 95% CI 0.338-2.169, P = 0.743, and HR = 2.39, 95% CI 0.93-6.111, P = 0.067, respectively). CONCLUSION: Results from the current analysis are in keeping with data from literature showing that pelvic irradiation and boost on positive nodes are effective approaches. Upfront surgical approach was not associated with better clinical outcomes.

Radiotherapy in prostate cancer after kidney transplant in 6 cases.

BACKGROUND: Patients who received a kidney transplant (KT) are described in literature as a group with a higher incidence of malignant neoplasms compared to the general population. Cancer development after KT has become a major issue, as a remarkable percentage of patients are diagnosed with cancer. Treatment of prostate cancer (PCa) in renal transplant recipients (RTRs) is a challenging issue that has been discussed by many authors over the years, but evidence is sparse and often includes conflicting reports. Among the therapeutic options for PCa in these patients, prostate irradiation represents a valuable alternative to surgery or other systemic therapies, as RTRs are often ineligible for these treatments. OBJECTIVE: To report six cases treated at our institution between 1998 and 2017 and discuss the available literature. METHODS: Patients' characteristics were reported along with biochemical status at diagnosis, type of immunosuppressive treatment, radiation therapy technique, and dose to transplanted kidney. RESULTS: Overall, prostate irradiation was delivered respecting the dose constraints and patients showed good tolerance with no reports of acute or late transplanted kidney injury. CONCLUSIONS: Our experience confirms that prostate radiotherapy for RTRs is feasible and effective and represents a valid option that should be considered by the multidisciplinary team.

Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial.

IMPORTANCE: Several studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients who are receiving cardiotoxic therapies. However, the optimal approach still represents a controversial issue. OBJECTIVE: To determine whether pharmacological cardioprevention could reduce subclinical heart damage in patients with breast cancer who are being treated with anthracycline-based chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: The SAFE trial was a 4-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at 8 oncology departments in Italy. It was a prespecified interim analysis on the first 174 patients who had completed cardiac assessment at 12 months. The study recruitment was conducted between July 2015 and June 2020. The interim analysis was performed in 2020. Patients were eligible for trial inclusion if they had indication to receive primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease were excluded. INTERVENTIONS: Cardioprotective therapy (bisoprolol, ramipril, or both drugs compared with placebo) was administered for 1 year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of ERBB2-positive patients. Doses for all groups were systematically up-titrated up to the daily target dose of bisoprolol (5 mg, once daily), ramipril (5 mg, once daily), and placebo, if tolerated. MAIN OUTCOMES AND MEASURES: The primary end point was defined as detection of any subclinical impairment (worsening ≥10%) in myocardial function and deformation measured with standard and 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). RESULTS: The analysis was performed on 174 women (median age, 48 years; range, 24-75 years) who had completed a cardiological assessment at 12 months and reached the end of treatment. At 12 months, 3D-LVEF worsened by 4.4% in placebo arm and 3.0%, 1.9%, 1.3% in the ramipril, bisoprolol, ramipril plus bisoprolol arms, respectively (P = .01). Global longitudinal strain worsened by 6.0% in placebo arm and 1.5% and 0.6% in the ramipril and bisoprolol arms, respectively, whereas it was unchanged (0.1% improvement) in the ramipril plus bisoprolol arm (P < .001). The number of patients showing a reduction of 10% or greater in 3D-LVEF was 8 (19%) in the placebo arm, 5 (11.5%) in the ramipril arm, 5 (11.4%) in the bisoprolol, arm and 3 (6.8%) in the ramipril plus bisoprolol arm; 15 patients (35.7%) who received placebo showed a 10% or greater worsening of GLS compared with 7 (15.9; ramipril), 6 (13.6%; bisoprolol), and 6 (13.6%; ramipril plus bisoprolol) (P = .03). CONCLUSIONS AND RELEVANCE: The interim analysis of this randomized clinical trials suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy-related LVEF decline and heart remodeling. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT2236806.

The NIPRO Study: An Observational, Retrospective, Multicenter Study on the Safety of the Radiotherapy and Immunotherapy Combination for Advanced-Stage NSCLC.

INTRODUCTION: In this observational, retrospective, multicenter study, we aimed to assess the safety of the combination of local metastasis-directed radiotherapy (RT) and immunotherapy (IT) in a cohort of advanced non-small-cell lung cancer (aNSCLC) patients. MATERIAL AND METHODS: We collected clinical data of aNSCLC patients who received concomitant RT and anti-PD-1/PD-L1 inhibitors in seven Italian centers from September 2015 to June 2019. Concomitant RT was defined as delivered ≤4 weeks before or after the first or last administration of immunotherapy, or within two consecutive cycles of ICI. All adverse events apparently related to RT and/or IT were graded according to the Common Terminology Criteria for Adverse Events, version 4.0, and reported in terms of incidence and severity as immune related or RT related, or combined. RESULTS: We analyzed the clinical charts of 187 patients. Median follow-up time was 23 months, and median overall survival was 16.5 months (range, 3-162). Thirteen patients developed pure RT-related side effects, and 43 patients (23.9%) developed immune-related side effects. No additive toxic effects were observed. A case of grade 5 pulmonary toxicity was recorded as a possible consequence of a combined effect. CONCLUSION: This analysis suggests that the combination of concomitant RT and anti-PD-1/PD-L1 agents is safe, and the two toxicity profiles are independent.

Outcome and prognostic factors for older patients undergoing radiosurgery for brain metastases.

PURPOSE: Older patients with brain metastases (BM) are often excluded from clinical trials. The aim of our study was to investigate the outcomes following Gamma Knife radiosurgery (GKRS) in young old (65-74 years) and very old (≥75 years) patients with BM. METHODS: Between October 2012 and October 2018, we treated 89 patients aged ≥65 years with GKRS. Patients were divided in two group: young old (YO) and very old (VO) patients. At baseline G8, Graded Prognostic Assessment (DS-GPA) and Basic Score for Brain Metastases (BSBM) were assessed for all patients. Survival analysis was estimated using the Kaplan-Meier (KM) method. Cox regression model was used to investigate the influence of significant factors on KM. RESULTS: Median age at the time of GKRS was 72.2 years (range 65-87). A mean of 2.52 lesions were treated per patient (range 1-14). Median overall survival (OS) for YO and VO patients was 14.2 and 15.7 months, respectively. At univariate analysis, there were no significant differences in OS between the two age groups. A high BSBM (p ≤ .0001) and a high DS-GPA score (p = .0069) were associated with longer survival. A low DS-GPA score was the most powerful independent factor for predicting short survival (HR 1.76, 95% CI 1.25-2.46, p = .001) at multivariate analysis. CONCLUSION: GKRS is a safe approach to treat BM in elderly patients. DS-GPA score represents an important prognostic factor for survival in elderly patients undergoing GKRS.

The role of postoperative radiotherapy for thymomas: a multicentric retrospective evaluation from three Italian centers and review of the literature.

BACKGROUND: Thymoma is a rare mediastinal neoplasia. Surgery is the backbone of the treatment, but the role of postoperative radiotherapy (PORT) remains controversial. We aimed to obtain data on survival and safety in patients treated with PORT in three different Italian institutions. METHODS: We retrospectively analyzed 183 consecutive patients who underwent surgery from 1981 to 2015. According to the Masaoka-Koga staging system, 39.3%, 32.7%, 18.6% and 9.8% patients were in stage I, II, III and IV of disease, respectively. PORT was indicated in 114 patients (62.3%), while 69 subjects underwent surgery alone. Complete resection was obtained in 68 patients who underwent PORT. Adverse events (AEs) were graded according to CTCAE v4.0. We analyzed the recent literature to describe the current reports on PORT for resected thymoma. RESULTS: Mean follow-up was 130 months (range, 3-417 months). Overall survival (OS) at 1-, 5- and 10-year from surgery was 98.3%, 90.2% and 69.7% respectively. One-, 5- and 10-year disease specific survival (DSS) was 98.9%, 92.3% and 89.8% respectively. Disease free survival (DFS) at 1, 5 and 10 years from surgery was 96.7%, 88.3% and 82.8% respectively. Univariate analysis showed that complete resection, cell histology A-AB-B1 and stages I-II were significant predictors of better DSS and DFS. Multivariate analysis showed that sex, R0 margins and WHO histology was independent prognostic factors. Among patients treated with PORT, a trend towards better OS was evident with Masaoka stage I-II (P=0.09). Patients with R0 margins treated with PORT showed better OS and DSS (P=0.05). No differences in DSS for performance status (P=0.70), WHO histology (P=0.19), paraneoplastic syndrome (P=0.23) and surgical procedure (P=0.53) were evident. Patients treated with PORT had a higher level of acute AEs compared to surgery alone, but none of these was graded ≥3. CONCLUSIONS: Our results confirmed that patients with incompletely resected thymoma had the worst OS and DSS. High grade acute toxicity was not different between PORT and surgery alone. Other trials reported a significant benefit in OS, DSS and DFS in stage IIb-IV thymoma treated with PORT.

Hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: a multi-centre comparative study.

Background: For decades, conventional fractionated whole breast irradiation (CF-WBI) was used after breast conserving surgery (BCS). Pivotal phase-3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients are often not treated with HF-WBI. The aim of this multi-centre comparative study is to confirm the safety of HF-WBI in a real-life series of younger patients.Material and methods: Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early-stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centres: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24 and 36 months.Results: At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute oedema, acute wet desquamation, chronic oedema, chronic erythema/pigmentation and breast fibrosis. At multivariate logistic analysis, hypofractionation was an independent significant factor for acute oedema, acute wet desquamation, and chronic oedema. There were not differences in tumour-related outcomes.Conclusions: HF-WBI showed significantly improved outcomes in terms of acute skin oedema, wet desquamation and chronic skin oedema. HF-WBI after BCS should be strongly encouraged to replace CF-WBI independently of age.

Clinical outcome of stereotactic body radiotherapy for lung-only oligometastatic head and neck squamous cell carcinoma: Is the deferral of systemic therapy a potential goal?

OBJECTIVES: Oligometastatic head and neck squamous cell carcinoma (HNSCC) is a rare entity with no evidence-based treatment recommendations available to support the use of local ablative therapies. The aim of our study was to report on the clinical benefit of stereotactic body radiotherapy (SBRT) for patients with lung-only oligometastases, defined by the presence of 1 to 5 pulmonary lesions. MATERIAL AND METHODS: SBRT was applied in case of single lesions deemed amenable to local treatment only ("de novo" pattern) or after first line chemotherapy at time of disease oligoprogression ("induced" pattern). To assess the potential deferral of systemic therapy in both time points, we analyzed time to progression (TTP) defined as the time from the last day of SBRT to disease progression or death from any cause. Cox regression analysis was performed to identify predictive factors of better outcome. RESULTS: Twenty-seven patients were retrospectively evaluated. The majority (81.5%) had HPV negative disease and a "de novo" oligometastatic pattern (78.6%). The median maximum lesion diameter and target size were 1.5 cm and 22.7 cc, respectively. At a median follow-up of 22 months (range 6-73), the median TTP was 10 months (95% CI: 9.5-21.1), with 1- and 2-year rates of 56.2% and 35%, respectively. The objective response rate at 3 months after SBRT was 75%. At multivariate analysis baseline T3/T4 stage had a HR for worse outcome of 5.38 (p = 0.033). Acute toxicity was minimal (G1/G2 of 14.8%). CONCLUSION: In properly selected oligometastatic patients, SBRT has potential for sustained deferral of systemic treatment.