Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation.

Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

Sinonasal Side Effects of Chemotherapy and/or Radiation Therapy for Head and Neck Cancer: A Literature Review.

Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy for head and neck cancer (HNC), with a specific focus on mucosal and olfactory disorders. A review of the English literature was performed using several databases (PubMed, Embase, Cochrane, Scopus). Fifty-six articles were included in qualitative synthesis: 28 assessed mucosal disorders (rhinitis or rhinosinusitis), 26 evaluated olfactory alterations, and 2 articles addressed both topics. The incidence and severity of olfactory dysfunction and chronic rhinosinusitis were highest at the end of radiotherapy and at three months after treatment and decreased gradually over time. Smell acuity deterioration and chronic rhinosinusitis seemed to be related to radiation dose on olfactory area and nasal cavities, but different degrees of recovery were observed. In conclusion, it is important to establish the severity of chronic rhinosinusitis and olfactory dysfunction in order to find strategies to support patients and improve their quality of life.

Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC.

Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.

Efficacy of low-dose radiotherapy (2 Gy × 2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas.

OBJECTIVES: To investigate the efficacy of a schedule of low-dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients. METHODS: We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I-IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan-Meier product-limit. RESULTS: Among 45 consecutively enrolled patients with a median age of 68 years (range 22-86), 26 (58%) were female. Thirty-one patients (69%) with a stage I-II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93, 92, 76 and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect. CONCLUSIONS: LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years. ADVANCES IN KNOWLEDGE: This study shows the efficacy of LDRT in the treatment of MALT and MZL.

Safety of lung stereotactic ablative radiotherapy for the functioning of cardiac implantable electronic devices.

BACKGROUND AND PURPOSE: The prevalence of patients with a cardiac implantable device (CIED) developing cancer and requiring a course of radiotherapy (RT) is increasing remarkably. Previously published reports agree that standard and conventionally fractionated RT is usually safe for CIEDs, but no "in-vivo" reports are available on the potential effects of thoracic stereotactic ablative radiotherapy (SABR) regimens to CIEDs functioning. The purpose of our study is therefore to evaluate the effects of SABR on CIEDs (pacemakers [PM] or implantable cardiac defibrillators [ICD]) in a cohort of patients affected by primary or metastatic lung lesions. MATERIALS AND METHODS: We retrospectively collected all CIED-bearing patients undergoing SABR between 2007 and 2019 at our Institution. All CIEDs were interrogated before and after the SABR course to check for any malfunction. Prescription dose, beam energy and maximum dose (Dmax) to CIEDs were retrieved for each patient. Electrical records of the CIEDs were reviewed by the medical records. RESULTS: Thirty-four consecutive patients (24 with a PM and 10 with an ICD), who underwent 38 separate SABR courses, were included in the study. Eight patients (24%) were PM-dependent. Prescription dose of SABR ranged 26-60 Gy in 1-8 fractions, with a photon energy ranging 6-to-10 MV (76.3% and 23.7%, respectively) and a median Dmax to CIEDs of 0.17 Gy (range 0.04-1.97 Gy). Electrical parameters were stable in post-treatment device programming visits and no transient or persistent alteration of the CIED function was recorded in any patient. No inappropriate interventions were recorded in the 10 ICD-bearing patients during the treatment fractions. CONCLUSIONS: Thoracic SABR proved to be safe for CIEDs when the dose is kept <2 Gy and the beam energy is ≤10 MV, irrespective of the pacing-dependency and of the CIED type.

Adoption of Expansion Margins to Reduce the Dose Received by the Coronary Arteries and the Risk of Cardiovascular Events in Lymphoma Patients.

PURPOSE: Mediastinal radiation therapy (RT) in patients with lymphoma implies involuntary coronary artery (CA) exposure, resulting in an increased risk of coronary artery disease (CAD). Accurate delineation of CAs may spare them from higher RT doses. However, heart motion affects the estimation of the dose received by CAs. An expansion margin (planning organ at risk volume [PRV]), encompassing the nearby area where CAs displace, may compensate for these uncertainties, reducing CA dose and CAD risk. Our study aimed to evaluate if a planning process optimized on CA-specific PRVs, rather than just on CAs, could provide any dosimetric or clinical benefit. METHODS AND MATERIALS: Forty patients receiving RT for mediastinal lymphomas were included. We contoured left main trunk, left anterior descending, left circumflex, and right coronary arteries. An isotropic PRV was then applied to all CAs, in accordance with literature data. A comparison was then performed by optimizing treatment plans either on CAs or on PRVs, to detect any difference in CA sparing in terms of maximum (Dmax), median (Dmed), and mean (Dmean) dose. We then investigated, through risk modeling, if any dosimetric benefit obtained with the PRV-related optimization process could translate to a lower risk of ischemic complications. RESULTS: Plan optimization on PRVs demonstrated a significant dose reduction (range, 7%-9%) in Dmax, Dmed, and Dmean for the whole coronary tree, and even higher dose reductions when vessels were located 5- to 20-mm from PTV (range, 13%-15%), especially for left main trunk and left circumflex (range, 16%-21%). This translated to a mean risk reduction of developing CAD of 12% (P < .01), which increased to 17% when CAs were located 5- to 20-mm from PTV. CONCLUSIONS: Integration of CA-related PRVs in the optimization process reduces the dose received by CAs and translates to a meaningful prevention of CAD risk in patients with lymphoma treated with mediastinal RT.

Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer.

Oral mucositis (OM) is a common acute side effect during radiotherapy treatments for head and neck cancer (HNC), with a potential impact on patient's compliance to therapy, quality of life (QoL) and clinical outcomes. Its timely and appropriate management is of paramount importance. Several quantitative scoring scales are available to properly assess OM and its influence on patient-reported outcomes (PROs) and QoL. We prospectively assessed OM in a cohort of HNC patients submitted to radiation using the Oral Mucositis Assessment Scale (OMAS), while its impact on PROs and QoL was evaluated employing the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN) and the Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-HN). Evaluation of OMAS scores highlighted a progressive increase in OM during treatment and a partial recovery after the end of radiation. These trends were correlated to PROs and QoL as evaluated with OMWQ-HN and FACT-HN questionnaires. In the present study, we provided a quantitative assessment of OM, PROs and QoL in HNC patient undergoing radiotherapy, potentially useful for future comparison.

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.