Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

Clinical Outcomes and Toxicity of CT-guided High Dose-rate Brachytherapy in Women With Locally-advanced Cervical Cancer.

BACKGROUND/AIM: To evaluate the outcome and toxicities in patients with locally advanced cervical cancer (LACC) treated with radiochemotherapy and intracavitary brachytherapy. PATIENTS AND METHODS: This study included 67 patients with LACC treated between 2010 and 2018. The most represented stage was FIGO IIB. The patients were treated with external beam radiotherapy (EBRT) to the pelvis and boost to the cervix and parametrials. Concomitant chemotherapy (CHT) with cisplatin (CDDP) 40 mg/mq was planned. Subsequently, the patients underwent CT-based endouterine brachytherapy (BT). The response was evaluated at 3 months with PET-CT and/or pelvic magnetic resonance imaging (MRI). Since then, the patients have been followed with clinical instrumental controls every 4 months for the first 2 years and every 6 months for the following 3 years. Local response was assessed with pelvic MRI and/or PET-CT scan at the end of intracavitary BT) according to RECIST 1.1 criteria. RESULTS: The median duration of treatment was 55 days (range=40-73 days). The prescription dose to the planning target volume (PTV) was delivered in 25 to 30 (median 28) daily fractions. The EBRT median dose to the pelvis and gross tumor volume were 50.4 Gy (range=45-56.25) and 61.6 Gy (range=45-70.4), respectively. The 1-year, 2-year, 3-year, and 5-year overall survival rates were 92.44%, 80.81%, 78.84%, and 76.45% respectively. The actuarial 1-year, 2-year, 3-year, and 5-year disease-free survival rates were 89.5%, 83.6%, 81%, and 78.2% respectively. CONCLUSION: This study analyzed acute and chronic toxicity, survival, and local control in cervical cancer patients treated with IMRT followed by CT-planned high dose rate-brachytherapy. Patients demonstrated satisfactory outcomes and incidence of acute and late toxicities.

Resilience in Radiotherapy Services During the COVID-19 Emergency: Collaboration Between the Regional Radiation Oncology Departments of Lazio, Abruzzo and Molise.

AIM: Radiation therapy is a cornerstone of oncological treatment and oncological patients show greater risk of developing complications related to COVID-19 infection. Stringent social restrictions have ensured a significant reduction in the spread of the virus, but also gave rise to a number of critical issues for radiation oncology wards. For this reason, the Directors of the Radiation Oncology Departments (RODs) of Lazio, Abruzzo and Molise regions shared their experience and ideas in order to create a common document that may assist in facing the negative impacts of the pandemic on radiation oncology wards and patients. PATIENTS AND METHODS: The study was conducted according to the Estimate-Talk-Estimate method. Five issues were proposed and rated. Among approved issues, statements were proposed anonymously, then harmonized and finally voted on according to a Likert scale from 1 to 9. Those for which an agreement of 7-9 was observed were finally approved. RESULTS: The document was developed with 42 statements dealing about safety measures for patients and staff, organization of clinical and work activities, usage of Information Technology systems for meetings/smart working. An agreement was recorded for 34 statements. CONCLUSION: This document sets out some recommendations for RODs and can provide valuable management information for Oncological Radiotherapy wards.

Clinical implication in the use of the AAA algorithm versus the AXB in nasopharyngeal carcinomas by comparison of TCP and NTCP values.

PURPOSE: Retrospective analysis of volumetric modulated arc therapy treatment plans to investigate qualitative, possible, clinical consequences of the use of AAA versus AXB in nasopharyngeal cancer (NPC) cases. METHODS: The dose distribution of 26 treatment plans, produced using RapidArc technique and AAA algorithm, were recalculated using AXB and the same number of monitor units provided by AAA and clinically delivered to each patient. The potential clinical effect of dosimetric differences in the planning target volume (PTV) and in organs at risk (OAR) were evaluated by comparing TCP and NTCP values. The Wilcoxon Signed Rank test was used for statistical comparison of all results obtained from the use of the two algorithms. RESULTS: The poorer coverage of the PTV, with higher prescribed dose, was reflected in the TCP, which was significantly lower when AXB was used, the median value was 81.55% (range: 74.90, 88.60%) and 84.10% (range: 77.70, 89.90%) for AAA (p < 0.001). OAR mean dose was lower in the AXB recalculated plan than the AAA plan and the difference was statistically significant for all the structures. The NTCP for developing mandible necrosis showed the largest median percentage difference between AAA and AXB (56.6%), the NTCP of risk for larynx edema of Grade ≥ 2 followed with 12.2%. CONCLUSIONS: Differences in dose distribution of NPC treatment plans recalculated with AXB are of clinical significance in those situations where the PTV and OAR involve air or bone, media in which AXB has been shown to more accurately represent the true dose distribution. The availability of AXB algorithm could improve patient dose estimation, increasing the data consistency of clinical trials.

Predictive Role of ERCC1 Expression in Head and Neck Squamous Cell Carcinoma Patients Treated with Surgery and Adjuvant Cisplatin-Based Chemoradiation.

OBJECTIVE: ERCC1 (excision repair cross-complementation group 1) expression predicts survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation. In order to evaluate the predictive role in the adjuvant setting, we investigated ERCC1 expression in radically resected HNSCC patients who underwent surgery and cisplatin chemoradiation. METHODS: ERCC1 expression levels were determined by immunohistochemistry in primary tumor tissues from 48 patients with stage III-IV cancers. The median follow-up was 38.5 months (range: 5-121). RESULTS: High ERCC1 expression was observed in 36 (75%) patients. Univariate analysis showed that patients with high levels of ERCC1 had significantly worse disease-free survival and overall survival (OS) than patients with low levels (HR = 7.15; 95% CI, 1.68-30.35; p = 0.008 and HR = 9.90; 95% CI, 1.33-73.96; p = 0.025, respectively). In the multivariate analysis, high ERCC1 expression (HR = 7.36; 95% CI, 1.72-31.4; p = 0.007) together with high-risk category (HR = 2.69; 95% CI, 1.01-7.18; p = 0.048) were the best predictors for relapse. High ERCC1 expression was the only unfavorable independent determinant for OS (HR = 9.53; 95% CI, 1.27-71.35; p = 0.028). CONCLUSIONS: This investigation suggests that ERCC1 expression might be useful to predict prognosis in radically resected HNSCC patients treated with surgery and chemoradiation.

Comparison between the ideal reference dose level and the actual reference dose level from clinical 3D radiotherapy treatment plans.

PURPOSE: Retrospective study of 3D clinical treatment plans based on radiobiological considerations in the choice of the reference dose level from tumor dose-volume histograms. METHODS AND MATERIALS: When a radiation oncologist evaluates the 3D dose distribution calculated by a treatment planning system, a decision must be made on the percentage dose level at which the prescribed dose should be delivered. Much effort is dedicated to deliver a dose as uniform as possible to the tumor volume. However due to the presence of critical organs, the result may be a rather inhomogeneous dose distribution throughout the tumor volume. In this study we use a formulation of tumor control probability (TCP) based on the linear quadratic model and on a parameter, the F factor. The F factor allows one to write TCP, from the heterogeneous dose distribution (TCP{(epsilon(j),D(j))}), as a function of TCP under condition of homogeneous irradiation of tumor volume (V) with dose D (TCP(V,D)). We used the expression of the F factor to calculate the "ideal" percentage dose level (iDL(r)) to be used as reference level for the prescribed dose D delivery, so as to render TCP{(epsilon(j),D(j))} equal to TCP(V,D). The 3D dose distributions of 53 clinical treatment plans were re-evaluated to derive the iDL(r) and to compare it with the one (D(tp)L) to which the dose was actually administered. RESULTS: For the majority of prostate treatments, we observed a low overdosing following the choice of a D(tp)L lower than the iDL(r.) While for the breast and head-and-neck treatments, the method showed that in many cases we underdosed choosing a D(tp)L greater than the iDL(r). The maximum difference between the iDL(r) and the D(tp)L was -3.24% for one of the head-and-neck treatments. CONCLUSIONS: Using the TCP model, the probability of tumor control is compromised following an incorrect choice of D(tp)L; so we conclude that the application of the F factor is an effective tool and clinical aid to derive the optimal reference dose level from the dose-volume histogram (DVH) of each treatment plan.

Dose and volume impact on radiation-induced xerostomia.

Radiation-induced xerostomia consists in the chronic dryness of the mouth caused by parotid gland irradiation. Parotid glands produce approximately 60% of saliva while the rest is secreted by submandibular and accessory salivary glands. Methods of measuring the salivary output are essentially represented by 99mTc-pertechnate scintigraphy or simpler albeit less accurate methods in stimulated or unstimulated saliva. There are subjective and objective criteria of classification and grading of the secretion of saliva. Radiation-induced xerostomia, namely the residual salivary gland function is evidently associated with the mean dose absorbed. The salivary output tends to decrease after the end of radiotherapy. The partial dose-volume is substantially correlated with the mean dose to the whole gland. As for ipsilateral irradiation for head and neck cancer, conformal RT or IMRT allow to spare the contralateral parotid gland without increasing the risk of contralateral nodal recurrences. The monitoring system of late toxicity used by the authors is presented.

Transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival.

BACKGROUND/AIMS: Transarterial chemoembolization is widely used for palliative treatment of hepatocellular carcinoma, but patient's characteristics associated with maximal benefit are still undefined. METHODOLOGY: In 81 cirrhotic patients with unresectable hepatocellular carcinoma, who underwent transarterial chemoembolization, variables correlated with survival were studied. In 46/81, the antipyrine metabolism test has been performed before and 72 hours after first transarterial chemoembolization. RESULTS: Mean overall survival of whole population was 22 months. One-, two-, and three-year survival rates were respectively 85%, 38.6%, and 18.1%. Better survival was observed in those patients who received more than one treatment (p = 0.016), while no relationship was found with treatment response, drug used, or number of lobes involved. Univariate analysis of the subgroup with antipyrine pharmacokinetic data revealed a significant relation between survival and baseline albumin (p = 0.039), total cholesterol (p = 0.036), AST (p = 0.017), log of total bilirubin (p = 0.017), and Child-Pugh class (p = 0.029), but not with parameters of antipyrine metabolism. Antipyrine metabolism was not significantly modified by transarterial chemoembolization in the subgroup tested before and after the first treatment. Using Cox regression analysis and selecting AST and log of total bilirubin, a prognostic index was defined: prognostic index 0.006 (AST-83.044) + 0.638 [log of total bilirubin-0.1175]. One-, two-, and three-year survival rates were respectively 92%, 59.2%, and 29.6% for the patient group with prognostic index < 0, and 76%, 14.3%, and 4.8% for the group with prognostic index > 0 (p < 0.01). CONCLUSIONS: Transarterial chemoembolization is a safe procedure and appears beneficial for those patients with a good functional hepatic reserve. The antipyrine metabolism test does not provide any additional prognostic information.

Biological factors and therapeutic modulation in radiotherapy of head and neck cancer.

The most recent clinical studies are increasingly concerned about the molecular factors in terms of prognosis, predictivity of response to treatments and development of novel, targeted therapeutic strategies. An integrated diagnostic and prognostic approach is envisaged where molecular biology with the study of biological markers "integrates" TNM to enhance the control of primary disease, resulting in a prolonged disease-free overall survival, earlier and effective control of locoregional progression and better quality of life (organ and function preservation). The prognostic or predictive role of the response to treatment for some markers (p53, EGFR, cyclin D1, telomerase activity) is defined in part in head and neck tumors. More statistically relevant data are necessary to establish which of these factors can permit a better selection of candidates for more aggressive or molecular targeted therapies or for a closer follow-up, thus contributing to the change of the natural history of these tumors.

Pain in osseous metastases: results of radiotherapy.

Seventy-nine patients with osseous metastases were prospectively evaluated bone pain. The evaluation of pain has been accomplished using the Keele Scale system. All cases have been treated with radiotherapy. The therapeutic response for analgesic effect has been evaluated in complete response (CR) when total disappearance of pain was present; in partial response (PR) with the reduction of at least 1 point on the Keele Scale: in non-responsive (NR) when patients showed worsening or no change in pain symptomatology during or following therapy. 51.8% have presented complete response, 36.8% partial response and 11.3% no response. The global response (CR + PR) has been 88.6%. This response was evaluated in relation to fractionating daily dose of radiotherapy and minimum dose necessary for analgesia.