High dose proton and photon-based radiation therapy for 213 liver lesions: a multi-institutional dosimetric comparison with a clinical perspective.

BACKGROUND: Stereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported. METHODS: Primary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV. RESULTS: 213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients. CONCLUSIONS: Cyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off.

Adoption of Hybrid MRI-Linac Systems for the Treatment of Brain Tumors: A Systematic Review of the Current Literature Regarding Clinical and Technical Features.

BACKGROUND: Possible advantages of magnetic resonance (MR)-guided radiation therapy (MRgRT) for the treatment of brain tumors include improved definition of treatment volumes and organs at risk (OARs) that could allow margin reductions, resulting in limited dose to the OARs and/or dose escalation to target volumes. Recently, hybrid systems integrating a linear accelerator and an magnetic resonance imaging (MRI) scan (MRI-linacs, MRL) have been introduced, that could potentially lead to a fully MRI-based treatment workflow. METHODS: We performed a systematic review of the published literature regarding the adoption of MRL for the treatment of primary or secondary brain tumors (last update November 3, 2022), retrieving a total of 2487 records; after a selection based on title and abstracts, the full text of 74 articles was analyzed, finally resulting in the 52 papers included in this review. RESULTS AND DISCUSSION: Several solutions have been implemented to achieve a paradigm shift from CT-based radiotherapy to MRgRT, such as the management of geometric integrity and the definition of synthetic CT models that estimate electron density. Multiple sequences have been optimized to acquire images with adequate quality with on-board MR scanner in limited times. Various sophisticated algorithms have been developed to compensate the impact of magnetic field on dose distribution and calculate daily adaptive plans in a few minutes with satisfactory dosimetric parameters for the treatment of primary brain tumors and cerebral metastases. Dosimetric studies and preliminary clinical experiences demonstrated the feasibility of treating brain lesions with MRL. CONCLUSIONS: The adoption of an MRI-only workflow is feasible and could offer several advantages for the treatment of brain tumors, including superior image quality for lesions and OARs and the possibility to adapt the treatment plan on the basis of daily MRI. The growing body of clinical data will clarify the potential benefit in terms of toxicity and response to treatment.

Image-guided radiotherapy (IGRT) in Lombardy, Italy: a survey by the Lombardy section of the Italian Association of Radiotherapy and Clinical Oncology (AIRO-Lombardy).

BACKGROUND: Image-guided radiation therapy (IGRT) has changed clinical practice. We proposed a survey to radiotherapy centers in Lombardy to picture the current clinical practice of its use. RESEARCH DESIGN AND METHODS: The survey consisted of 32 multiple-choice questions, divided into five topics: type of hospital, patients treated in 2019, number of LINACs; presence of protocols and staff involved in IGRT; IGRT in stereotaxis; IGRT in non-stereotactic treatments; availability of medical and technical staff. RESULTS: Twenty-seven directors answered (77%). Most centers (74%) have produced protocols to ensure uniformity in the IGRT process. The most widely used IGRT modality (92%) is cone-beam CT. Daily IGRT control is favored for prostate (100%), head and neck (87%), and lung (78%) neoplasms. The resident doctors can always perform supervised IGRT matching in only six centers. Radiation therapists perform IGRT controls only for some sites in 12 cases (44%) and always in 9 cases (33%). Radiation oncologists are present in real time, in most cases. CONCLUSIONS: Today, IGRT can be considered standard practice but at the price of more time-consuming procedures. A balance between a fully physician-controlled process and an increased role for specifically trained RTTs is actively being sought.

Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2.

BACKGROUND: Extensive research effort has been devoted to investigating the link between inflammation and PCa. However, this relationship remains unclear and controversial. The aim of our multi-center study was to investigate this association by histologically evaluating the distribution of PI and PCA in prostate biopsy cores from patients of eight referral centers in Italy. RESULTS: We evaluated 2220 cores from 197 patients; all the frustules were re-evaluated by dedicated pathologists retrospectively. Pathologists assigned IRANI scores and determined the positions of PIs; pathologists also re-evaluated the presence of PCa and relative ISUP grade. PCa was recorded in 749/2220 (33.7%). We divided this sample into a PCa PI group (634/749 cores [84.7%]) and a non-PCa + PI group (1157/1471 cores [78.7%]). We observed a statistically significant difference in the presence of inflammation among cores with cancer (p < 0.01). Moreover, periglandular inflammation was higher in the cores with neoplasia, while stromal inflammation was higher in cores without neoplasia (38.5% vs. 31.1% and 55.4% vs. 63.5% p < 0.01). CONCLUSIONS: In our experience, there is evidence of an association between PI and PCa at a tissue level. Further studies are needed to confirm our findings and to identify patients who might benefit from target therapies to prevent PCa occurrence and/or progression.

Early results of PRO-EPI: PROspective multicenter observational study on elective pelvic nodes irradiation in patients with intermediate/high/very high-risk non-metastatic prostate cancer submitted to radical, adjuvant, or salvage radiotherapy with or without concomitant androgen deprivation therapy.

Simple Summary: Although radiotherapy plays a fundamental role in the management of intermediate/high/very high-risk non-metastatic prostatic cancer (IHR-nmPca), there is still no consensus on the optimal treatment strategy in this setting. Remarkably, the role of elective nodal irradiation (ENI) is still highly controversial. The PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) was designed to provide "real life" data regarding the patterns of care for IHR-nmPca. Forty-three Italian Radiation Oncology centers participated in the PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) project, with 1029 patients enrolled. In this preliminary analysis, we longitudinally evaluated the impact of Elective Nodal Irradiation (ENI) and radiotherapy features on toxicity and quality of life (QoL). Six months follow-up data were available for 913 patients and 12 months data for 762 patients. Elective Nodal Irradiation was given to 506 patients (48.9%). Volumetric Intensity-Modulated Radiation Therapy (IMRT) was adopted in more than 77% of patients and Image-Guided Radiation Therapy (IGRT) in 84.4%. Androgen deprivation therapy (ADT) was administered to the majority of patients (68.3%), and it was associated to ENI in 408 cases (81.1%). Toxicity was mostly mild and reversible and IGRT resulted in a significant reduction of rectal toxicity, although a non-significant trend toward increased urinary toxicity was observed. No statistically significant differences in QoL and toxicity were seen in patients treated with or without ENI. The adoption of IGRT is widespread and increasing and could reduce treatment toxicity. ENI is not yet the standard treatment, but it is performed in a growing fraction of cases and not resulting into an increase in toxicity or in a deterioration of QoL. Further analyses are needed to clarify the long-term toxicity profile and the impact of ENI on survival.

Anal squamous cell carcinoma: Impact of radiochemotherapy evolution over years and an explorative analysis of MRI prediction of tumor response in a mono-institutional series of 131 patients.

Introduction: Radiochemotherapy (RCHT) for the treatment of anal squamous cell carcinoma (ASCC) has evolved dramatically, also thanks to intensity-modulated RT (IMRT) and 3D image guidance (3D IGRT). Despite most patients presenting fair outcomes, unmet needs still exist. Predictors of poor tumor response are lacking; acute toxicity remains challenging; and local relapse remains the main pattern of failure. Patients and methods: Between 2010 and 2020, ASCC stages I-III treated with 3D conformal radiotherapy or IMRT and CDDP-5FU or Mytomicine-5FU CHT were identified. Image guidance accepted included 2D IGRT or 3D IGRT. The study endpoints included freedom from locoregional recurrence (FFLR), colostomy free survival (CFS), freedom from distant metastasis (FFDM), overall survival (OS), and acute and late toxicity as measured by common terminology criteria for adverse events (CTCAE) version 5.0. An exploratory analysis was performed to identify possible radiomic predictors of tumor response. Feature extraction and data analysis were performed in Python™, while other statistics were performed using SPSS® v.26.0 software (IBM®). Results: A total of 131 patients were identified. After a median FU of 52 months, 83 patients (63.4%) were alive. A total of 35 patients (26.7%) experienced locoregional failure, while 31 patients (23.7%) relapsed with distant metastasis. Five year FFLR, CFS, DMFS and PS resulted 72.3%, 80.1%, 74.5% and 64.6%. In multivariate analysis, 2D IGRT was associated with poorer FFLR, OS, and CFS (HR 4.5, 4.1, and 5.6, respectively); 3DcRT was associated with poorer OS and CFS (HR 3.1 and 6.6, respectively). IMRT reduced severe acute gastro-intestinal (GI) and severe skin acute toxicity in comparison with 3DcRT. In the exploratory analysis, the risk of relapse depended on a combination of three parameters: Total Energy, Gray Level Size Zone Matrix's Large Area High Gray Level Emphasis (GLSZM's LAHGLE), and GTV volume. Conclusions: Advances in radiotherapy have independently improved the prognosis of ASCC patients over years while decreasing acute GI and skin toxicity. IMRT and daily 3D image guidance may be considered standard of care in the management of ASCC. A combination of three pre-treatment MRI parameters such as low signal intensity (SI), high GLSZM's LAHGLE, and GTV volume could be integrated in risk stratification to identify candidates for RT dose-escalation to be enrolled in clinical trials.

Patterns of recurrences in sinonasal cancers undergoing an endoscopic surgery-based treatment: Results of the MUSES* on 940 patients: *MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

OBJECTIVES: The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence. MATERIALS AND METHODS: All patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence. RESULTS: The 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes. CONCLUSION: This study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences.

Effect of Degarelix Administration on Bone Health in Prostate Cancer Patients Without Bone Metastases. The Blade Study.

CONTEXT: As patients are now living with prostate cancer for longer, the long-term impact of hormonal treatment on bone health is an increasingly debated subject. OBJECTIVE: To characterize the changes in bone mineral density (BMD) and bone turnover markers after degarelix administration in prostate cancer patients without bone metastases. To explore the predictive role of body composition on treatment induced bone loss. METHODS: BMD and body composition (lean body mass, fat body mass, and appendicular mass index [ALMI]) were assessed by dual X-ray absorptiometry on study entry and after 12 months of degarelix therapy. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline, and 6 and 12 months. RESULTS: Twenty-nine patients entered the study. Degarelix administration was associated with a significant decrease in BMD after 12 months (2.4% reduction from baseline at lumbar spine). Serum CTX and ALP increased significantly (median increase from baseline 99% and 19.3%, respectively). An inverse correlation was observed between ALMI and CTX, but not ALP, at both baseline (Pearson r = -0.62, P < .0001) and month 12 (Pearson r = -0.41, P = .032). Moreover, a significant inverse correlation between changes in ALMI and CTX at 12 months (Pearson r = -0.43, P = .019) and a direct relationship between changes of ALMI and ALP (Pearson r = 0.44, P = .016) during degarelix therapy were observed. CONCLUSION: Degarelix administration is associated with a significant decrease in BMD and increase in bone turnover markers. ALMI is a promising predictor of bone loss in prostate cancer patients receiving androgen deprivation therapy, and ALMI changes during therapy are associated with bone turnover derangement favoring bone quality alterations.

Chemo-radiotherapy plus durvalumab for loco-regional relapse of resected NSCLC.

BACKGROUND: tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient's life expectancy. The optimal treatment strategy for loco-regional recurrences developing after surgical resection in patients with non-small-cell lung cancer (NSCLC) is not established yet. This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery. METHODS:  We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse. RESULTS: Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47-78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%. CONCLUSIONS: In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery.

Stratification of Oligometastatic Prostate Cancer Patients by Liquid Biopsy: Clinical Insights from a Pilot Study.

We propose a pilot, prospective, translational study with the aim of identifying possible molecular markers underlying metastatic prostate cancer (PC) evolution with the use of liquid biopsy. Twenty-eight castrate sensitive, oligometastatic PC patients undergoing bone and/or nodal stereotactic body radiotherapy (SBRT) were recruited. Peripheral blood samples were collected before the commencement of SBRT, then they were processed for circulating cell free DNA (cfDNA) extraction. Deep targeted sequencing was performed using a custom gene panel. The primary endpoint was to identify differences in the molecular contribution between the oligometastatic and polymetastatic evolution of PC to same-first oligo-recurrent disease presentation. Seventy-seven mutations were detected in 25/28 cfDNA samples: ATM in 14 (50%) cases, BRCA2 11 (39%), BRCA1 6 (21%), AR 13 (46%), ETV4, and ETV6 2 (7%). SBRT failure was associated with an increased risk of harboring the BRCA1 mutation (OR 10.5) (p = 0.043). The median cfDNA concentration was 24.02 ng/mL for ATM mutation carriers vs. 40.04 ng/mL for non-carriers (p = 0.039). Real-time molecular characterization of oligometastatic PC may allow for the identification of a true oligometastatic phenotype, with a stable disease over a long time being more likely to benefit from local, curative treatments or the achievement of long-term disease control. A prospective validation of our promising findings is desirable for a better understanding of the real impact of liquid biopsy in detecting tumor aggressiveness and clonal evolution.

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.

Impact of stereotactic body radiotherapy vs palliative radiotherapy on oncologic outcomes of patients with metastatic kidney cancer concomitantly treated with immune checkpoint inhibitors: a preliminary, multicentre experience.

PURPOSE: To explore the benefit yielded by radiotherapy (RT), we report a series of metastatic renal cell carcinoma (RCC) patients treated with concomitant RT plus Nivolumab. METHODS/PATIENTS: Patients undergoing Nivolumab treatment plus concomitant RT (ablative or palliative) were included. RT was defined Ablative if >5 Gy/fraction were delivered. RESULTS: Ablative RT intent was the only independent predictor of both progression free and overall survival (HR 3.51, 95% CI 1.6-7.5, p = 0.0012 and HR 2.8, 95% CI 0.99-8.07, p = 0.05, respectively). CONCLUSION: Ablative RT may improve oncologic outcomes in selected patients with metastatic RCC treated with Nivolumab as compared to palliative RT.

RR Myelo POINT: A Retrospective Single-Center Study Assessing the Role of Radiotherapy in the Management of Multiple Myeloma and Possible Interactions with Concurrent Systemic Treatment.

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/ß ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.

PSMA-guided metastases directed therapy for bone castration sensitive oligometastatic prostate cancer: a multi-institutional study.

To assess the outcomes of a cohort of bone oligometastatic prostate cancer patients treated with PSMA-PET guided stereotactic body radiotherapy (SBRT). From April 2017 to January 2021, 40 patients with oligorecurrent prostate cancer detected by PSMA-PET were treated with SBRT for bone oligometastases. Concurrent androgen deprivation therapy was an exclusion criterion. A total of 56 prostate cancer bone oligometastases were included in the present analysis. In 28 patients (70%), oligometastatic disease presented as a single lesion, two lesions in 22.5%, three lesions in 5%, four lesions in 2.5%. 30.3% were spine-metastases, while 69.7% were non-spine metastases. SBRT was delivered for a median dose of 30 Gy (24-40 Gy) in 3-5 fractions, with a median EQD2 = 85 Gy2 (64.3-138.9Gy2). With a median follow-up of 22 months (range 2-48 months), local control (LC) 1- and 2-years rates were 96.3% and 93.9%, while distant progression-free survival (DPFS) rates were 45.3% and 27%. At multivariate analysis, the lower PSA nadir value after SBRT remained significantly related to better DPFS rates (p = 0.03). In 7 patients, a second SBRT course was proposed with concurrent ADT, while 11 patients, due to polymetastatic spread, received ADT alone, resulting in 1- and 2-years ADT-free survival rates of 67.5% and 61.8%. At multivariate analysis, a lower number of treated oligometastases maintained a correlation with higher ADT-free survival rates (p = 0.04). In our experience, PSMA-PET guided SBRT resulted in excellent results in terms of clinical outcomes, representing a helpful tool with the aim to delay the start of ADT.

Stereotactic Radiotherapy and Androgen Deprivation Therapy for Localized Prostate Cancer: A Retrospective Mono-institutional Experience.

BACKGROUND/AIM: Stereotactic radiotherapy (SRT) is an effective treatment for localized prostate cancer. However, is it not clear whether the addition of androgen deprivation therapy (ADT) to SRT is beneficial. The aim of this study was to analyze the outcomes of a series of patients treated with SRT plus ADT for localized prostate cancer. PATIENTS AND METHODS: Patients were treated with SRT with 42 Gy in 7 fractions with volumetric-modulated arc therapy plus Image Guided Radiotherapy (V-MAT IGRT) technique. ADT was administered to patients with intermediate unfavorable- and high-risk disease. Study endpoints were biochemical disease-free survival (bDFS), overall survival (OS), acute and late toxicity and patient-reported outcomes (PROs) using international prostate cancer symptoms scale (IPSS) and international index of erectile function (IIEF). RESULTS: A total of 170 consecutive patients were identified, of which 49 (28.8%) with low-risk, 15 (8.8%) with favorable intermediate-risk 76 (44.7%) with unfavorable intermediate-risk and 30 (17.6%) with high-risk class. All patients of unfavorable intermediate- and high-risk groups were administered LHRH analogue concurrently to SRT and for at least 6 months. Patients with unfavorable intermediate- and high-risk presented a 5-year bDFS of 81.7% and 76.9%, respectively. CONCLUSION: SRT consisting of 42 Gy in seven fractions with short-term ADT represents a safe and effective treatment for unfavorable intermediate and high risk prostate cancer. Our results support the need of high quality studies to test the efficacy of ADT combined with SRT for unfavorable intermediate- and high-risk localized prostate cancer.

'Le Roi est mort, vive le Roi': New Roles of Radiotherapy in the Treatment of Lymphomas in Combination With Immunotherapy.

BACKGROUND: immunotherapy (IT), including checkpoint inhibitors (CIs) and Chimeric Antigen Receptor T cell therapy (CAR-T) revolutionized the treatment of relapsing or refractory (r/r) lymphoma. Several preliminary experiences evaluated concomitant administration of radiotherapy and IT. METHODS: we performed a systematic review of current literature as of March 30, 2020. A total of 1090 records was retrieved, 42 articles were selected on the basis of title and abstract and, after the removal of analyses with no original data or insufficient clinical information, 28 papers were included in the review. RESULTS: previous studies were mostly represented by case reports/series or small cohorts. Nonetheless, combination of radiotherapy and CIs or CAR-T led to promising outcomes, resulting in extremely high rates of complete response and improving progression free and overall survival compared with data from recent clinical trials. Combination of RT and CIs had a fair toxicity profile with no reports of severe side effects. Within the limits of the small cohorts retrieved, RT seems a superior option compared with systemic treatment as a 'bridge' to CAR-T and could as well reduce severe complications rates. Radiotherapy could elicit immune response against lymphoma, as demonstrated by multiple cases of abscopal effect and its inclusion in anti-neoplastic vaccines protocols. CONCLUSION: The results of this review warrant the evaluation of combination of RT and immunotherapy in larger and preferably prospective and randomized cohorts to confirm these preliminary impressive outcomes. The optimal dose, fractionation and timing of RT still have to be clarified.

Almost one year of COVID-19 pandemic: how radiotherapy centers have counteracted its impact on cancer treatment in Lombardy, Italy. CODRAL/AIRO-L study.

Lombardy has represented the Italian and European epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Although most clinical efforts within hospitals were diverted towards the care of virally infected patients, therapies for patients with cancer, including radiotherapy (RT), have continued. During both the first and second pandemic waves, several national and regional organizations provided Italian and Lombardian RT departments with detailed guidelines aimed at ensuring safe treatments during the pandemic. The spread of infection among patients and personnel was limited by adopting strict measures, including triage procedures, interpersonal distance, and adequate implementation of personal protective equipment (PPE). Screening procedures addressed to both the healthcare workforce and patients, such as periodic nasopharyngeal swabs, have allowed the early identification of asymptomatic or pauci-symptomatic COVID-19 cases, thus reducing the spread of the infection. Prevention of infection was deemed of paramount importance to protect both patients and personnel and to ensure the availability of a minimum number of staff members to maintain clinical activity. The choice of treating COVID-19-positive patients has represented a matter of debate, and the risk of oncologic progression has been weighted against the risk of infection of personnel and other patients. Such risk was minimized by creating dedicated paths, reserving time slots, applying intensified cleaning procedures, and supplying personnel and staff with appropriate PPE. Remote working of research staff, medical physicists, and, in some cases, radiation oncologists has prevented overcrowding of shared spaces, reducing infection spread.

Radiotherapy at oligoprogression for metastatic castration-resistant prostate cancer patients: a multi-institutional analysis.

PURPOSE: To retrospectively estimate the impact of radiotherapy as a progression-directed therapy (PDT) in oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) patients under androgen receptor-target therapy (ARTT). MATERIALS AND METHODS: mCRPC patients are treated with PDT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events v4.0. Survival analysis was performed using the Kaplan-Meier method; univariate and multivariate analyses were performed. RESULTS: Fifty-seven patients were analyzed. The median follow-up after PDT was 25.2 months (interquartile, 17.1-44.5). One-year NEST-free survival, r-PFS and OS were 49.8%, 50.4% and 82.1%, respectively. At multivariate analysis, polymetastatic condition at diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) (HR 2.82, p = 0.004) and PSA doubling time at diagnosis of mCRPC (HR 2.76, p = 0.006) were associated with NEST-free survival. The same variables were associated with r-PFS (HR 2.32, p = 0.021; HR 2.24, p = 0.021). One patient developed late grade ≥ 2 toxicity. CONCLUSION: Our study shows that radiotherapy in oligoprogressive mCRPC is safe, is effective and seems to prolong the efficacy of ARTT in patients who otherwise would have gone systemic treatment switch, positively affecting disease progression. Prospective trials are needed.

Ductal prostate cancer: Clinical features and outcomes from a multicenter retrospective analysis and overview of the current literature.

Objective: The aim of the study is to evaluate clinical features and outcomes after different therapeutic strategies for ductal prostate adenocarcinoma (DPC), a rare but aggressive subtype of invasive prostate cancer (PCa) accounting for, in the pure and mixed form, 1% or less and 5% or less, respectively, of all the newly diagnosed PCa. Materials and methods: Patients with a proven diagnosis of DPC undergoing surgery, radiotherapy, and androgen deprivation therapy, alone or in combination, were considered for this multicenter, retrospective study. The study assessed overall survival (OS), disease-free survival (DFS), and age-related disease-specific survival. Results: Eighty-one patients met the study inclusion criteria. Pure DPC was found in 29 patients (36%) and mixed ductal-acinar-PCa in 52 patients (64%). After a median follow-up of 63 months (range, 3-206 months), 3- and 5-year OS rates were 84% and 67%, respectively, and 3- and 5-year DFS rates were 54% and 34%, respectively. There were no significant differences in OS or DFS between the pure and mixed DPC groups. Pure DPC was associated with a higher rate of metastatic disease at onset. Patients 74 years or younger had better disease-specific survival (p=0.0019). A subgroup analysis favored radiotherapy as the primary treatment for nonmetastatic, organ-confined DPC (3- and 5-year DFS of 80% and 50%, respectively, compared with 5-year DFS of 35% for surgical patients; p = 0.023). Conclusions: Our study found DPC to be rarer, more aggressive, more likely to metastasize, and have a worse prognosis than the common acinar variant, especially in its pure form. Multicenter series are encouraged to obtain large data sets, or propensity score matching analyses with patients with conventional PCa are desirable to understand the best therapeutic approach and improve outcomes.