Radiation-Related Dysphagia: From Pathophysiology to Clinical Aspects

In Western countries, head and neck cancers (HNCs) account for about 5% of all tumors. Due to tumor locations at the aero-digestive crossroad, patients frequently suffer from swallowing dysfunction caused both by primary cancer (baseline dysphagia) and cancer therapies (treatment-related dysphagia). In this regard, radiation-induced dysphagia represents a real “Achille’s heel” which historically occurs in more than 50% of patients and can lead to a malnutritional status and an increased risk of aspiration pneumonia. In fact radiotherapy, by restricting the driving pressure of the bolus through the pharynx and/or limiting the opening of the cricopharyngeal muscle, leads to a post-swallowing pharyngeal residue that may spill into the airway causing ab ingestis pneumonia. On the contrary, an organ preservation strategy should provide both the highest tumor control probability (TCP) and the minimum function impairment with the subsequent maximum therapeutic index gain. In this regard, intensity-modulated RT (IMRT) might reduce the probability of postradiation dysphagia by producing concave dose distributions with better avoidance of several critical structures, such as swallowing organs at risk (SWOARs), which might result in better functional outcomes. Similarly, a prompt swallowing rehabilitation provided before, during, and soon after radiotherapy plays an important role in improving oncologic swallowing outcomes

Bevacizumab for the Treatment of Radiation-Induced Cerebral Necrosis: A Systematic Review of the Literature

Radiation necrosis (RN) of brain tissue is a serious late complication of brain irradiation and recently bevacizumab has been suggested as treatment option of RN. There is a lack of data in the literature regarding the effectiveness of bevacizumab for the treatment of RN. The purpose of this review was to perform a comprehensive analysis of all reported cases using bevacizumab for the treatment of brain RN. In September 2016, we performed a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. The research for the review was conducted using a combination of the keywords “radiation necrosis”, “radiotherapy” and “bevacizumab” alongside the fields comprising article title, abstract and keywords. Randomized trials, non-randomized trials, prospective studies, retrospective studies and single case reports were included in the review. Our research generated 21 studies and 125 cases where bevacizumab had been used for the treatment of RN. The median follow-up was 8 months and the most frequent bevacizumab dose used was 7.5 mg/kg for 2 weeks with a median of four cycles. Low-dose bevacizumab resulted in effectiveness with improvement in both clinical and radiographic response. The median decrease in T1 contrast enhancement and in T2/FLAIR signal abnormality was 64% and 60%, respectively. A reduction in steroidal therapy was observed in majority of patients treated. Based on the data of our review, bevacizumab appears to be a promising agent for the treatment of brain RN. Future prospective studies are required to evaluate the role of bevacizumab in RN and to define the optimal scheduling, dosage and duration of therapy

The effectiveness of bevacizumab in radionecrosis after radiosurgery of a single brain metastasis

Radionecrosis (RN) of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticosteroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73- years-old women affected by a primary nonsmall cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy

Non-melanoma skin cancer treated with high-doserate brachytherapy and Valencia applicator in elderly patients: a retrospective case series

Purpose: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. Basal cell carcinoma and squamous cell carcinoma are the two most common subtypes of NMSC. The aim of this study was to estimate tumour control, toxicity, and aesthetic events in elderly patients treated with high-dose-rate (HDR) brachytherapy (BT) using Valencia applicator. Material and methods: From January 2012 to May 2015, 57 lesions in 39 elderly eligible patients were enrolled. All the lesions had a diameter ≤ 25 mm (median: 12.5 mm) and a depth ≤ 4 mm. The appropriate Valencia applicator, 2 or 3 cm in diameter was used. The prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) in 48 lesions (group A), and 50 Gy in 10 fractions (5 Gy/fraction) in 9 lesions (group B), delivered 2/3 times a week. The biological effective dose (BED) was 60 Gy and 75 Gy, respectively. Results: After median follow-up of 12 months, 96.25% lesions showed a complete response and only two cases presented partial remission. Radiation Therapy Oncology Group – European Organization for Research and Treatment of Cancer (RTOG/EORTC) G 1-2 acute toxicities were observed in 63.2% of the lesions: 56.3% in group A and 77.7% in group B. Late G1-G2 toxicities was observed in 19.3% of the lesions: 18.8% in group A and 22.2% in group B, respectively. No G3 or higher acute or late toxicities occurred. In 86% of the lesions, an excellent cosmetic result was observed (87.5% in group A and 77.8% in group B). Six lesions had a good cosmetic outcome and only 2.3% presented a fair cosmetic impact. Conclusions: The treatment of NMSC with HDR-BT using Valencia surface applicator is effective with excellent and good cosmetics results in elderly patients. The hypofractionated course appears effective and no statistical differences were observed between the two groups analysed

Radiotherapy in the COVID-19 Pandemic Era

Background/Aim: In 2020, because of coronavirus pandemic, medical activities changed. The aim of this report is to compare the volumes of Pisa radiotherapy activities from March 9th to May 31st, 2020, with the same period in 2019. Patients and Methods: We analyzed the activity of our Unit to evaluate how logistics changes, related to the COVID-19 epidemic, impacted on volumes of radiotherapy (RT) activity and on the number of cases of COVID-19 infections observed in healthcare professionals and patients. Results: The total number of first-time visits between March-May 2020 was reduced by 18%, probably due to delays in diagnosis and histological tests as well as the temporary closure of the operating rooms. None of the healthcare professionals and only two patients contracted the infection. Conclusion: We were able to treat all patients referred to our hospital and we were able to reduce risk of infection for both our patients and healthcare staff, guaranteeing continuum of care for our oncological patien

Role of perfusion CT in the evaluation of functional primary tumour response after radiochemotherapy in head and neck cancer: Preliminary findings

Objective: To report the initial results of a prospective study aimed at evaluating the CT perfusion parameter changes (ΔPCTp) of the primary tumour after radiochemotherapy (RCT) in head and neck cancer (HNC) and to correlate with positron emission tomography (PET)/CT response. Methods: Eligibility criteria included HNC (Stage III-IV) candidates for RCT. Patients underwent perfusion CT (PCT) at baseline and at 3 weeks and 3 months after treatment. Blood volume, blood flow, mean transit time (MTT) and permeability surface (PS) product were computed. Moreover, PET/CT was performed at baseline and 3 months after treatment. The ΔPCTp were evaluated between baseline and 3-week/3-month evaluations, whereas PET/CT response was based on the maximum standardized uptake value changes according to the European Organization for Research and Treatment of Cancer criteria. Results: Between July 2012 and July 2015, 25 patients were enrolled. A significant reduction of all CT tumour perfusion parameters (PCTp) was observed from the baseline to after RCT (p<0.001). Specifically, a significant reduction was shown at 3 weeks for all PCTp except MTT (from 6.18 to 5.14s; p=0.722). Differently, a significant reduction of all PCTp (p<0.001) including MTT (from 6.18 to 2.24s; p=0.001) was shown at 3 months. Moreover, the reduction of PS resulted in a significant prediction of PET/CT response at 3 months (p=0.037) with the trend also at 3 weeks (p=0.099) at the multivariate analysis. Conclusion: Our preliminary findings seem to show that almost all PCTp are significantly reduced after RCT, whereas PS seems to come out as the strongest factor in predicting the PET/CT response. Advances in knowledge: This article provides information on the potential useful role of PCT in evaluating tumour response after both early and late RCT

Results of a survey on elderly head and neck cancer patients on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Problem. Over the years, evidence-based data and technical improvements have consolidated the central role of radiation therapy (RT) in head and neck cancer (HNC) treatment, even in the elderly. This survey aimed to describe the management of the elderly HNC patients among Italian Radiation Oncology Departments (RODs) and provide possible suggestions for improvement. Method of study. An online survey based on 43 questions was sent to RODs via email. For each RODs, a radiation oncologist with expertise in HNC was invited to answer questions addressing his/her demographic data, ROD multidisciplinary unit (MU) organisation and ROD management policy in elderly HNC patients. Results. In total, 68 RODs answered, representing centres located in 16 Italian regions. MU was considered the core of HNC patient management in almost all the country. However, in many RODs, there was minimal access to a routinely comprehensive geriatric assessment at diagnosis. Most treatments were reported by respondents as curative (89% on average) and the preferred treatment technique was intensity modulated radiation therapy (IMRT). A considerable variation between RODs was found for RT target volumes. There was a relation between the specialist’s years of experience and type of concomitant systemic therapy prescribed. Conclusions. Substantial differences in elderly HNC management have been found, especially concerning patient clinical evaluation and target volume delineation. This survey shows the necessity to design a prospective national trial to provide a uniform treatment strategy and define an effective patient-centred approach

The role of clinicopathologic and molecular prognostic factors in the post-mastectomy radiotherapy (PMRT): a retrospective analysis of 912 patients

OBJECTIVE: To assess the association of clinicopathologic and molecular features with loco-regional recurrence (LRR) in post-mastectomy breast cancer patients with or without adjuvant radiotherapy (PMRT). PATIENTS AND METHODS: We retrospectively reviewed data of patients undergone to mastectomy followed or not by PMRT between January 2004 and June 2013. The patients were divided according to clinicopathologic and molecular sub-classification features. LRR and Cancer Specific Survival (CSS) were calculated using the Kaplan-Meier method; the prognostic factors were compared using long-rank tests and Cox regression model. RESULTS: A total of 912 patients underwent to mastectomy of whom 269 (29.5%) followed by PMRT and 643 (70.5%) not; among the PMRT group, 77 underwent to the chest wall (CW) and 202 to the chest wall and lymphatic drainage (CWLD) irradiation. The median follow-up was 54 months (range, 3-118). No significant difference in terms of LRR and CSS was found between non-PMRT and PMRT group (p=0.175; and p=0.628). The multivariate analysis of LRR for patients who did not undergo PMRT showed a significant correlation with the presence of extracapsular extension (ECE) (p=0.049), Ki-67>30% (p=0.048) and triple negative status (p=0.001). In the PMRT group, triple negative status resulted as the only variable significantly correlated to LRR (p=0.006) at the multivariate analysis and T-stage also showed a trend to significance (p=0.073). Finally, no difference in LRR control was shown between CW and CWLD-PMRT (p=0.078). CONCLUSIONS: After mastectomy ECE, a cut off of Ki-67>30% and triple negative status werestrictly correlated with LRR regardless of clinicopathologic stage. PMRT has a positive impact in decreasing LRR in patients with this molecular profile. Besides, CW might represent a valid option for patients with one to three positive nodes

Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature

Purpose: The incidence of non-melanoma skin cancer (NMSC) has been increasing over the past 30 years. There are different treatment options and surgical excision is the most frequent treatment due to its low rates of recurrence. Radiotherapy is an effective alternative of surgery, and brachytherapy (BT) might be a better therapeutic option due to high radiation dose concentration to the tumor with rapid dose fall-off resulting in normal tissues sparing. The aim of this review was to evaluate the local control, toxicity, and cosmetic outcomes in NMSC treated with high-dose-rate BT (HDR-BT). Material and methods: In May 2016, a systematic search of bibliographic database of PubMed, Web of Science, Scopus, and Cochrane Library with a combination of key words of “skin cancer”, “high dose rate brachytherapy”,“squamous cell carcinoma”, “basal cell carcinoma”, and “non melanoma skin cancer“ was performed. In this systematic review, we included randomized trials, non-randomized trials, prospective and retrospective studies in patients affected by NMSC treated with HDR-BT. Results: Our searches generated a total of 85 results, and through a process of screening, 10 publications were selected for the review. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 97%). Cosmetic outcome was reported in seven study and consisted in an excellent and good cosmetic results in 94.8% of cases. Conclusions: Based on the review data, we can conclude that the treatment of NMSC with HDR-BT is effective with excellent and good cosmetics results, even in elderly patients. The hypofractionated course appears effective with very good local disease control. More data with large-scale randomized controlled trials are needed to assess the efficacy and safety of brachytherapy