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.

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.

Peritransplant Radiation Therapy in Patients With Refractory or Relapsed Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant: Long-Term Results of a Retrospective Study of the Fondazione Italiana Linfomi.

PURPOSE: In this multicenter collaboration, we report real-world data in the largest published series of long-term outcomes for patients with relapsed/refractory (r/r) Hodgkin lymphoma (HL) treated with peritransplant radiation therapy (pt-RT) and high-dose chemotherapy with autologous stem cell transplant (ASCT). METHODS AND MATERIALS: We conducted a retrospective analysis including data from 12 institutions. Eligibility required histologic diagnosis of HL, receipt of ASCT plus pt-RT between 2004 and 2014 for r/r HL, and age ≥18 years at the time of ASCT. All patients received salvage chemotherapy for maximum debulking before ASCT. Metabolic responses were scored according to the Lugano Classification. The primary endpoint was overall survival (OS). Univariate and multivariate Cox proportional hazards were calculated to estimate the effect of covariates on patients' outcome. RESULTS: One hundred thirty-one patients were eligible: 68 were male (52%), and median age at ASCT was 32 years (range, 18-70). At the time of diagnosis with r/r HL, 92 patients (70%) had limited (stage I-II) disease, and 10 patients (8%) had bulky disease. Pt-RT was given pre-ASCT in 32 patients (24%) and post-ASCT in 99 (76%); median prescribed dose was 30.6 Gy (range, 20-44 Gy). With median follow-up of 60 months, 3- and 5-year OS were 84% and 77%, while 3- and 5-year progression-free survival were 75% and 72%, respectively. On univariate and multivariate analysis, advanced stage at relapse (hazard ratio [HR], 2.18; P = .04), irradiation of >3 sites (HR, 3.69; P = .01), and incomplete metabolic response after salvage chemotherapy (HR, 2.24; P = .01) had a negative effect on OS. The sequencing of pt-RT (pre- vs post-ASCT) did not affect outcomes. CONCLUSIONS: Overall, the addition of pt-RT to ASCT for patients with r/r HL is associated with very good outcomes. Limited relapsed disease with ≤3 sites involved and achievement of complete metabolic response after salvage chemotherapy were predictive of more favorable prognosis.

Prostate Cancer Treatment-Related Toxicity: Comparison between 3D-Conformal Radiation Therapy (3D-CRT) and Volumetric Modulated Arc Therapy (VMAT) Techniques.

Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan−Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance.

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.

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.

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.

'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.

Universal testing for COVID-19 in patients undergoing cancer treatment during the second outbreak in Brescia.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) has been overwhelming on patients with cancer, who may be at higher risk of developing severe disease. During the second COVID-19 outbreak in Italy, we planned universal microbiologic screening for patients scheduled for antineoplastic treatment. METHODS: All patients with planned active treatment at Brescia University Radiation Oncology Department were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA with repeated nasopharyngeal swabs (NPS) from October 31, 2020. Treatment continuation, suspension, or delay was modulated for patients testing positive according to clinical presentation. RESULTS: From October 31, 2020, to February 6, 2021, 636 patients were enrolled and 1243 NPS were performed, of which 28 (2.25%) were positive. The infection rate was 2.52%; 81.3% of the patients with a positive NPS were asymptomatic, 2 had mild disease, and 1 severe disease that led to death. All patients already on treatment with mild or asymptomatic COVID-19 carried on the therapy with no or minimal delay. Median delay for patients with infection detected before treatment start was 16.5 days. CONCLUSIONS: Detected incidence of COVID-19 was lower during the second outbreak in our patients (2.52% vs 3.23%), despite the extensive testing schedule, and substantiates the high rate of asymptomatic infections and the low mortality among patients with COVID-19 (6.3% vs 38.5% during the first outbreak). Universal SARS-CoV-2 screening for all patients with planned treatment might allow early identification of patients with COVID-19, resulting in timely management that could improve clinical outcomes and prevent spread of the infection.

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.

Nasopharyngeal cancer in non-endemic areas: Impact of treatment intensity within a large retrospective multicentre cohort.

AIM: Recommendations for managing patients with nasopharyngeal carcinoma (NPC) in non-endemic areas are largely derived from studies conducted in endemic areas. We analysed the impact of treatment approaches on survival in non-endemic areas. METHODS: In an international, multicentre, retrospective study, we analyse consecutive patients with NPC diagnosed between 2004 and 2017 in 36 hospitals from 11 countries. Treatment was categorised as non-intensive (NIT), including radiotherapy alone or concomitant chemoradiotherapy (cCRT), and intensive (IT) including cCRT preceded by and/or followed by chemotherapy (CT). The impact of IT on overall survival (OS) and disease-free survival (DFS) was adjusted for all the available potential confounders. RESULTS: Overall, 1021 and 1113 patients were eligible for overall survival (OS) and disease-free survival (DFS) analyses, respectively; 501 and 554 with Epstein Barr-encoded RNA (EBER) status available. In the whole group, 5-year OS was 84% and DFS 65%. The use of NIT was associated with a risk of death or recurrence 1.37 times higher than patients receiving IT. Patients submitted to NIT and induction CT + concurrent concomitant chemo and three-dimensional Conformal Radiation Therapy (3DCRT) had a risk of death or recurrence 1.5 and 1.7 times higher than patients treated with induction CT + cCRT with intensity-modulated radiotherapy (IMRT), respectively. The IT had no impact on OS in neither patients with EBER+ nor in patients with EBER-; IT showed better DFS in EBER+ but not in patients with EBER-. CONCLUSIONS: In low-incidence areas, patients with NPC treated with induction CT followed by concurrent IMRT cCRT achieved the highest DFS rate. The benefit of IT on DFS was restricted to patients with EBER+, suggesting that additional therapy offers no advantages in EBER- cases.

Role of radiotherapy to bulky sites of advanced Hodgkin lymphoma treated with ABVD: final results of FIL HD0801 trial.

The role of consolidation radiotherapy (RT) for bulky lesions is controversial in patients with advanced-stage Hodgkin lymphoma who achieve complete metabolic response (CMR) after doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD)-based chemotherapy. We present the final results of the Fondazione Italiana Linfomi HD0801 trial, which investigated the potential benefit of RT in that setting. In this phase 3 randomized study, patients with a bulky lesion at baseline (a mass with largest diameter ≥5 cm) who have CMR after 2 and 6 ABVD cycles were randomly assigned 1:1 to RT vs observation (OBS) with a primary endpoint of event-free survival (EFS) at 2 years. The sample size was calculated estimating an EFS improvement for RT of 20% (from 60% to 80%). The secondary end point was progression-free survival (PFS). One hundred sixteen patients met the inclusion criteria and were randomly assigned to RT or OBS. Intention-to-treat (ITT) analysis showed a 2-year EFS of 87.8% vs 85.8% for RT vs OBS (hazard ratio [HR], 1.5; 95% confidence interval [CI], 0.6-3.5; P = .34). At 2 years, ITT-PFS was 91.3% vs 85.8% (HR, 1.2; 95% CI, 0.5-3; P = .7). Patients in CMR randomly assigned to OBS had a good outcome, and the primary end point of a 20% benefit in EFS for RT was not met. However, the sample size was underpowered to detect a benefit of 10% or less, keeping open the question of a potential, more limited role of RT in this setting. This trial was registered at www.clinicaltrials.gov as #NCT00784537.

A Systematic Review on Intensity Modulated Radiation Therapy for Mediastinal Hodgkin's Lymphoma.

BACKGROUND: Secondary malignant neoplasms (SMNs) and cardiovascular diseases induced by chemotherapy and radiotherapy represent the main cause of excess mortality for early-stage Hodgkin lymphoma patients, especially when the mediastinum is involved. Conformal radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) could allow a reduction of the dose to the organs-at-risk (OARs) and therefore limit long-term toxicity. METHODS: We performed a systematic review of the current literature regarding comparisons between IMRT and conventional photon beam radiotherapy, or between different IMRT techniques, for the treatment of mediastinal lymphoma. RESULTS AND CONCLUSIONS: IMRT allows a substantial reduction of the volumes of OARs exposed to high doses, reducing the risk of long-term toxicity. This benefit is conterbalanced by the increase of volumes receiving low doses, that could potentially increase the risk of SMNs. Treatment planning should be personalized on patient and disease characteristics. Dedicated techniques such as "butterfly" VMAT often provide the best trade-off.

Gene Expression Profiling of Olfactory Neuroblastoma Helps Identify Prognostic Pathways and Define Potentially Therapeutic Targets.

Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the transcriptional pathways altered in ONB and correlate them with pathological features and clinical outcomes. We analyze 32 ONB patients treated with curative intent at two independent institutions from 2001 to 2019 for whom there is available pathologic and clinical data. We perform gene expression profiling on primary ONB samples and carry out functional enrichment analysis to investigate the key pathways associated with disease-free survival (DFS). The median age is 53.5 years; all patients undergo surgery and a pure endoscopic approach is adopted in the majority of cases (81.2%). Most patients have advanced disease (stages III-IV, 81.2%) and 84.4% undergo adjuvant (chemo)radiotherapy. The median follow-up is 35 months; 11 (26.8%) patients relapse. Clinical characteristics (gender, stage and Hyams' grade) are not associated with the outcomes. In contrast, TGF-beta binding, EMT, IFN-alpha response, angiogenesis, IL2-STAT5 and IL6-JAK-STAT3 signaling pathways are enriched in patients experiencing recurrence, and significantly associated with shorter DFS. Clustering of transcriptional profiles according to pathological features indicates two distinct molecular groups, defined by either cytokeratin-positive or -negative immunostaining. Definition of the characterizing ONB transcriptomic pathways may pave the way towards tailored treatment approaches.

Impact of Gastrointestinal Side Effects on Patients' Reported Quality of Life Trajectories after Radiotherapy for Prostate Cancer: Data from the Prospective, Observational Pros-IT CNR Study.

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients' reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04-7.08; OR = 2.17, 95% CI 1.22-3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06-2.67; OR = 2.57, 95% CI 1.70-3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects.

Prognosis and management of recurrent and/or metastatic head and neck adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare tumor, usually arising in the salivary gland, accounting for 1% of all head and neck cancers. ACC may have a long-term poor prognosis, as about 40% of radically treated patients will recur locoregionally and up to 60% will develop distant metastasis. Factors influencing risk of recurrence have been well studied, but few data exist about prognostic factors in Recurrent/Metastatic (RM) setting. Moreover, treatment of RM ACC is often a challenge for clinicians, in the context of a rare disease, which may have an indolent clinical behavior or less frequently a quicker growth and with a paucity of available clinical trials. This review critically analyzes pathological and molecular prognostic factors in RM ACC and make an overview on actual therapeutic choices and future direction of therapy. Recognized prognostic factors in RM ACC are the presence and site of distant metastasis (lung vs other), the presence of nodal metastasis and of extranodal extension, skull base recurrence, disease free interval, lymphovascular invasion, solid histotypes and grading of disease, and the presence of mutation of NOTCH1 family, PI3K, and TP53. Due to disappointing results with chemotherapy, new approaches are under study, also on the basis of biomolecular research. Ongoing clinical trials are evaluating treatment targeting MYB and NOTCH1 alterations, immunotherapy or combination of targeted treatments and immune checkpoint inhibitors.