Home-based pulmonary rehabilitation in patients undergoing (chemo)radiation therapy for unresectable lung cancer: a prospective explorative study.

AIMS: The prevention of pulmonary toxicity is an important goal for patient candidate to radiation therapy for lung cancer. There is a lack of evidence on the role of exercise training for patients with unresectable stage III lung cancer candidated to radical treatment. The aim of this study was to evaluate the feasibility of a home-based pulmonary rehabilitation (PR) program and to identify reliable tools in terms of respiratory function, exercise capacity and quality of life. METHODS: Patients' recruitment lasted from April 2020 till February 2022. The PR program was proposed concomitantly to radiation therapy to the first 20 patients (interventional group, IG), and the other 20 patients were identified as an observational group (OG). All patients were assessed at baseline (T0) and after 8 weeks (T2) with 6 minute walking test (6MWT), modified Borg Scale (mBORG), SF-36 questionnaire (SF-36) and pulmonary function test (PFT); after 4 weeks (T1), only SF-36 was administered. RESULTS: A decrease of 13.8 m in the walked-distance was registered in the OG between T0 and T2 (p = 0.083). Instead, an increase of 56.6 m in the distance walked was recorded in the IG between T0 and T2 (p ≤ 0.001). In the OG, the mBORG scores showed a negative trend. On the contrary, in the IG, these scores showed a slight improvement. In the OG, all the items of SF-36 scores decreased between T0 and T1. In the IG, an increased trend from T0 to T2 was observed for all the items of SF-36. No clinically significant variations were detected from baseline to T2 in both groups regarding PFT. CONCLUSION: The 6MWT, mBORG and SF-36 resulted as useful tools to assess the role of a PR program. A significant gain in functional exercise capacity and a prevention of the physiological impairment of QoL during radio(chemo)therapy was registered.

Postoperative radiotherapy for prostate cancer: the sooner the better and potential to reduce toxicity even further.

PURPOSE: To evaluate biochemical relapse-free survival (bRFS), overall survival (OS), late rectal and bladder toxicities in a retrospective single institution series, also applying an in-house software for biological dose calculation. METHODS: 258 patients submitted to radiotherapy after prostatectomy were considered. Differences between groups were calculated using the log-rank test and the relevant clinical and therapeutic variables were considered for multivariate analysis. PRODVH is an in-house system able to calculate mean dose-volume histograms (DVHs) of a series of patients, to convert them in biologically effective DVHs (BEDVHs) and allowing to compare them with ANOVA and t Student test. RESULTS: Adjuvant radiotherapy (ART) and salvage radiotherapy (SRT) were performed in 131 (50.8%) and 127 patients (49.2%). At multivariate analysis advanced T stage, androgen deprivation total (ADT) and SRT resulted as independent variables related to a worst bRFS (p = 0.019, 0.001 and 0.02), while GS > 7 and SRT affected negatively OS (p 0.047 and 0.039). High grade toxicity events occurred mainly in patients treated with 3-dimensional conformal radiotherapy (3DCRT) (proctitis p = 0.006; cystitis: p = 0.041). A significantly more favorable mean rectum BEDVH for patients with G0 or G1 rectal toxicity was shown (p < 0.001). Mean BEDVH for both bladder (p < 0.01) and rectum (p < 0.05) were also significantly better for volumetric modulated arc therapy-image guided radiotherapy (VMAT-IGRT) plans than for 3DCRT plans. CONCLUSION: ART is better than SRT in terms of bRFS and OS, particularly for more aggressive cases, advanced T stage and higher Gleason Score. Postoperative prostate cancer radiotherapy should be applied as soon as possible after surgery. The use of modern techniques such as VMAT-IGRT significantly reduces toxicity.

Artificial Intelligence-suggested Predictive Model of Survival in Patients Treated With Stereotactic Radiotherapy for Early Lung Cancer.

BACKGROUND/AIM: Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting. PATIENTS AND METHODS: Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts. RESULTS: Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2. CONCLUSION: The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively.

Unresectable stage III non-small cell lung cancer: could durvalumab be safe and effective in real-life clinical scenarios? Results of a single-center experience.

Introduction: The standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by consolidation durvalumab as shown in the PACIFIC trial. The purpose of this study is to evaluate clinical outcomes and toxicities regarding the use of durvalumab in a real clinical scenario. Methods: A single-center retrospective study was conducted on patients with a diagnosis of unresectable stage III NSCLC who underwent radical CRT followed or not by durvalumab. Tumor response after CRT, pattern of relapse, overall survival (OS) and progression-free survival (PFS), and toxicity profile were investigated. Results: Eighty-five patients met the inclusion criteria. The median age was 67 years (range 45-82 years). Fifty-two patients (61.2%) started sequential therapy with durvalumab. The main reason for excluding patients from the durvalumab treatment was the expression of PD-L1 < 1%. Only two patients presented a grade 4 or 5 pneumonitis. A median follow-up (FU) of 20 months has been reached. Forty-five patients (52.9%) had disease progression, and 21 (24.7%) had a distant progression. The addition of maintenance immunotherapy confirmed a clinical benefit in terms of OS and PFS. Two-year OS and PFS were respectively 69.4% and 54.4% in the durvalumab group and 47.9% and 24.2% in the no-durvalumab group (p = 0.015, p = 0.007). Conclusion: In this real-world study, patients treated with CRT plus durvalumab showed clinical outcomes and toxicities similar to the PACIFIC results. Maintenance immunotherapy after CRT has been shown to be safe and has increased the survival of patients in clinical practice.

Low-dose Lung Radiotherapy for COVID-19-related Pneumonia: Preliminary Results of the Italian Mono-institutional COLOR-19 Trial.

AIM: To evaluate the feasibility and tolerability of low-dose radiotherapy (LDRT) delivered to both lungs in the treatment of SARS-CoV-2-immune-mediated pneumonia in the COLOR-19 study (NCT0437747). PATIENTS AND METHODS: From May 2020 to April 2021 at Brescia University Radiation Oncology Department, three patients with COVID-19-related pneumonia were treated with LDRT according to the COLOR-19 protocol. All patients were treated with a single fraction at the average prescription dose of 0.7 Gy to both lungs. RESULTS: Three patients were enrolled (two males and one female, aged 61-81 years) and underwent LDRT. Despite LDRT being safely performed without significant side-effects, two patients died (one 81-year-old male due to septic shock secondary to Escherichia coli infection and one 79-year-old male, already in poor condition, due to worsening of COVID-19). The remaining female patient (61 years old) underwent LDRT for less severe COVID-19: her clinical condition and chest X-ray improved, and she was discharged home completely asymptomatic 27 days after hospital admission. Blood levels of C-reactive protein and ferritin generally decreased after LDRT. CONCLUSION: Early results of the COLOR-19 study demonstrate the feasibility of LDRT for therapy of COVID-19-related pneumonia; no conclusions on the efficacy have been reached due to poor accrual.

Prevention and management of acute esophageal toxicity during concomitant chemoradiotherapy for locally advanced lung cancer.

BACKGROUND: Standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concomitant chemoradiotherapy. The survival benefit of combined treatment is partially counterbalanced by an increased rate of acute esophageal toxicity. Several pharmaceutical products are available for prevention and management of esophagitis, including Faringel Plus. AIM: To assess the incidence and the grade, identify the correlations with clinical, dosimetric, and therapeutic variables, and analyse the role of Faringel Plus as a pharmaceutical preventive measure against acute esophageal toxicity. METHODS: Patients with LA-NSCLC treated with concomitant radiochemotherapy were retrospectively reviewed. Acute esophagitis and dysphagia were graded according to Common Terminology Criteria for Adverse Events version 5.0. Clinical, dosimetric, and therapeutic correlations were investigated using χ2 test. RESULTS: Among the 23 analysed patients, 18 (78.3%) and 1 (4.3%) developed G2 and G3 esophagitis, respectively; G1-2 dysphagia were reported in 11 cases (47.8%). No statistically significant correlation between the variables considered and acute esophageal toxicity was identified. In the group of patients who received Faringel Plus as preventive treatment (10 subjects, 43.5%), dysphagia presentation time was significantly longer (p = 0.038); esophagitis onset time was longer and symptoms duration was shorter. Faringel Plus allowed a reduction in the use of analgesic drugs. CONCLUSIONS: Acute mild esophageal toxicity was confirmed to be a common side effect in this setting. No clinical-dosimetric parameter has been demonstrated to be effective in predicting acute esophageal toxicity. The use of Faringel Plus appears effective as a therapeutic and prophylactic tool to manage acute esophageal toxicity.

Three weekly versus weekly concurrent cisplatin: safety propensity score analysis on 166 head and neck cancer patients.

BACKGROUND: Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m2/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m2/q1. METHODS: Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules. RESULTS: Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule. CONCLUSIONS: 3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients.

How Has Prostate Cancer Radiotherapy Changed in Italy between 2004 and 2011? An Analysis of the National Patterns-Of-Practice (POP) Database by the Uro-Oncology Study Group of the Italian Society of Radiotherapy and Clinical Oncology (AIRO).

BACKGROUND AND PURPOSE: Two previous "Patterns Of Practice" surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy (EBRT) between 1980 and 2003, established a "benchmark" Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies. METHODS: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III. RESULTS: More than 50% of POP III patients were classified as low or intermediate risk using D'Amico risk categories as in POP II; 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series; late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate- and high-risk patients treated with ≥ 76 Gy. CONCLUSIONS: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004-2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins >8 mm were associated with increased toxicity, again suggesting that IGRT-allowing for tighter margins-would reduce toxicity for dose escalated RT. These conclusions confirm the data obtained from randomized controlled studies.

Two months of radiation oncology in the heart of Italian "red zone" during COVID-19 pandemic: paving a safe path over thin ice.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) pandemic had an overwhelming impact on healthcare worldwide. Outstandingly, the aftermath on neoplastic patients is still largely unknown, and only isolated cases of COVID-19 during radiotherapy have been published. We will report the two-months experience of our Department, set in Lombardy "red-zone". METHODS: Data of 402 cancer patients undergoing active treatment from February 24 to April 24, 2020 were retrospectively reviewed; several indicators of the Department functioning were also analyzed. RESULTS: Dedicated measures allowed an overall limited reduction of the workload. Decrease of radiotherapy treatment number reached 17%, while the number of administration of systemic treatment and follow up evaluations kept constant. Conversely, new treatment planning faced substantial decline. Considering the patients, infection rate was 3.23% (13/402) and mortality 1.24% (5/402). Median age of COVID-19 patients was 69.7 years, the large majority were male and smokers (84.6%); lung cancer was the most common tumor type (61.5%), 84.6% of subjects were stage III-IV and 92.3% had comorbidities. Remarkably, 92.3% of the cases were detected before March 24. Globally, only 2.5% of ongoing treatments were suspended due to suspect or confirmed COVID-19 and 46.2% of positive patients carried on radiotherapy without interruption. Considering only the last month, infection rate among patients undergoing treatment precipitated to 0.43% (1/232) and no new contagions were reported within our staff. CONCLUSIONS: Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during SARS-Cov-2 pandemic by endorsing consistent preventive measures.

Cetuximab and Radiation Therapy Versus Cisplatin and Radiation Therapy for Locally Advanced Head and Neck Cancer: Long-Term Survival and Toxicity Outcomes of a Randomized Phase 2 Trial.

PURPOSE: This study describes the long-term survival and toxicity outcomes of a multicenter randomized phase 2 trial comparing radiation therapy (RT) plus cisplatin (CDDP) or cetuximab (CTX) as first line treatment in locally advanced head and neck cancer (LASCCHN). METHODS AND MATERIALS: Between January 2011 and August 2014, 70 patients were enrolled and randomized to receive RT plus weekly CDDP (40 mg/m2) or CTX (250 mg/m2 plus a loading dose of 400 mg/m2). This updated series focuses on late toxicities (graded by using Common Terminology Criteria for Adverse Events version 4.0) and long-term survival outcomes in terms of local control, overall survival, cancer-specific survival, and metastasis-free survival (MFS). A supplementary analysis based on human papilloma virus (HPV) status was also performed. RESULTS: No statistically significant difference was found in terms of late effects (xerostomia, fibrosis, mucosal atrophy, weight loss). In the CDDP arm and the CTX arm, 5-year local control rates were 67% and 48%; 5-year MFS rates were 83% and 97%; 5-year overall survival rates were 61% and 52%; and 5-year cancer-specific survival rates were 70% and 59%, respectively. None of these differences reached statistical significance. A subgroup analysis by HPV status and anatomic subsites revealed that in HPV+ oropharyngeal carcinoma, better survival was obtained in the CDDP arm (although statistical tests were not performed owing to the small sample size). Conversely, no statistically significant differences were observed in HPV- oropharyngeal carcinoma and other anatomic subsites, except for the confirmed better MFS rates of the CTX arm. CONCLUSIONS: Long-term results are in line with current literature suggesting that RT + CTX is inferior to RT + CDDP for the definitive treatment of LASCCHN. However, if not as an alternative to CDDP, CTX might still play a role in LASCCHN, particularly in HPV- cases.

Primary cutaneous non-Hodgkin lymphoma: results of a retrospective analysis in the light of the recent ILROG guidelines.

PURPOSE:: To analyze clinical outcome, local response, survival and toxicity in patients with primary cutaneous lymphoma (PCL) treated with radiotherapy. METHODS:: From 1995 to 2014, 112 patients were treated. B-cell lymphomas (CBCLs; n = 86) and T-cell lymphomas (CTCLs; n = 23) were analyzed separately. Clinical and therapeutic characteristics (age, sex, histology, primary treatment and radiotherapy modality) were related to response to treatment, survival and toxicity. RESULTS:: CBCLs were divided into 4 subgroups: marginal-zone lymphoma (n = 20), follicle center lymphoma (n = 32), diffuse large-cell lymphoma (DLBCL; n = 22) and DLBCL-leg type (n = 12). No significant correlation was found between doses and systemic treatments, extent of biopsy and number of lesions. DLBCL-leg type patients were older (p = 0.05), had disseminated disease (p = 0.034), and more frequently had local (p = 0.01) or systemic recurrence (p = 0.05). CTCLs were divided into 4 subgroups: α/ß CTCL (n = 3), nasal type CTCL (n = 0), γ/δ CTCL (n = 10) and mycosis fungoides (n = 10). Longer disease-free survival was observed in patients obtaining complete remission (p<0.001). CONCLUSIONS:: Radiotherapy is feasible, safe and effective for localized PCLs. The choice of dose is related to histological subgroups and the related prognoses. Survival results are very good also in relapsing disease. In advanced cutaneous lymphoma radiotherapy alone has mainly a role in symptom palliation.

Radiotherapy and Tyrosine Kinase Inhibitors in Stage IV Non-small Cell Lung Cancer: Real-life Experience.

AIM: To investigate the role of conventional radiotherapy (RT) and stereotactic body radiotherapy (SBRT) in patients with epidermal growth factor (EGFR)-mutant or anaplastic lymphoma kinase (ALK) rearrangement-positive metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty patients with EGFR-mutated or ALK rearrangement-positive NSCLC were treated at our Institution. Radiotherapy was delivered before, after or concomitantly with tyrosine kinase inhibitors (TKIs). Acute toxicities and overall survival (OS) were assessed. RESULTS: Radiotherapy was performed within 30 days before TKI, concomitantly with TKI and within 30 days after TKI in eight (16%), 33 (66%) and 9 (18%) cases, respectively. The median duration of TKI therapy in the whole series was 11.9 months. The median OS was 19.3 months and 1- and 2-year OS was 71.5% and 36.5%, respectively. The group treated with SBRT had a significant benefit in terms of OS (p=0.043). Only two grade 3 toxicities were reported. CONCLUSION: RT concomitantly or close to TKI administration in stage IV NSCLC was shown to be feasible and safe. Intriguing data on OS were also reported.

Light and shadows of a new technique: is photon total-skin irradiation using helical IMRT feasible, less complex and as toxic as the electrons one?

BACKGROUND: Radiotherapy is one of the standard treatments for cutaneous lymphoma and Total Skin Electrons Beam Irradiation (TSEBI) is generally used to treat diffuse cutaneous lymphoma and some cases of localized disease. Helical IMRT (HI) allows to treat complex target with optimal dose distribution and organ at risk sparing, so helical tomotherapy has been proposed as alternative technique to TSEBI but only one preliminary report has been published. METHODS: Three patients treated (from May 2013 to December 2014) with Helical IMRT, with a total dose between 24 and 30 Gy, were retrospectively evaluated. Data about dosimetric features, response and acute toxicity were registered and analyzed. Planned target coverage was compared with daily in vivo measures and dose calculation based on volumetric images used for set up evaluation as well. RESULTS: The patients had a mean measured surface fraction dose ranging from 1.54 Gy up to 2.0 Gy. A planned target dose ranging from 85 to 120% of prescription doses was obtained. All doses to Organs At Risk were within the required constraints. Particular attention was posed on "whole bone marrow" planned V10Gy, V12Gy and V20Gy values, ranging respectively between 23 and 43%, 20.1 and 38% and 9.8 and 24%. A comparison with the theoretical homologous values obtained with TSEBI has shown much lower values with TSEBI. Even if treatment was given in sequence to the skin of the upper and lower hemi-body, all the patients had anaemia, requiring blood transfusions, leukopenia and thrombocytopenia. CONCLUSION: Based on our limited results TSEBI should still be considered the standard method to treat total skin because of its pattern of acute and late toxicities and the dose distribution. In this particular case the better target coverage obtained with HI can be paid in terms of worse toxicity. Helical IMRT can instead be considered optimal in treating large, convex, cutaneous areas where it is difficult to use multiple electrons fields in relation with the clinical results and the limited and reversible toxicities.

Analysis of Circulating Tumor Cells in Prostate Cancer Patients at PSA Recurrence and Review of the Literature.

BACKGROUND: Circulating tumor cells have been described in prostate cancer patients at diagnosis and in the metastatic phase but little is known on their role at biochemical PSA recurrence. PATIENTS AND METHODS: Patients radically cured with either prostatectomy or radiotherapy were sequentially included at PSA recurrence. The presence of CTCs was evaluated by the CellSearch system. RESULTS: Twenty-nine patients were accrued at PSA recurrence. Median PSA at recurrence was 7.2 ng/ml (range=3.86-51.0 ng/ml). The median time to PSA progression was 4.66 years (range=0.1-16 years). CTCs were detected in one patient (3%) with low numbers (1 CTC/7.5 ml). CONCLUSION: In patients radically cured for prostate cancer at biochemical recurrence, CTCs are detected at very low levels in a minority of patients. Further studies are required to investigate alternative methods of CTC detection and the possible role of the bone marrow pre-metastatic niche at biochemical recurrence.