Patient-Reported Outcomes After Swallowing (SWOARs)-Sparing IMRT in Head and Neck Cancers: Primary Results from a Prospective Study Endorsed by the Head and Neck Study Group (HNSG) of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

OBJECTIVES: To prospectively investigate changes in M.D. Anderson Dysphagia Inventory (MDADI) scores in patients affected by naso- and oropharynx cancer after definitive radiochemotherapy (ChemoRT) using swallowing organs at risk (SWOARs)-sparing IMRT. METHODS: MDADI questionnaires were collected at baseline and at 6 and 12 months after treatment. MDADI scores were categorized as follows: ≥ 80 "optimal," 80-60 "adequate," < 60 "poor" deglutition-related quality of life (QoL) group, and dichotomized as "optimal" vs "adequate/poor" for the analysis. A mean MDADI composite (MDADI-C) change of 10 points was considered as minimal clinically important difference (MCID). RESULTS: Sixty-three patients were enrolled of which 47 were considered for the analysis. At baseline, 26 (55%) were "optimal" and 21 (45%) were "adequate/poor." The mean baseline MDADI-C score was 93.6 dropping to 81 at 6 months (p = 0.013) and slightly rising to 85.5 at 12 months (p = 0.321) for the "optimal" group. Indeed, the mean baseline MDADI-C score was 64.3 rising to 77.5 at 6 months (p = 0.006) and stabilizing at 76 at 12 months (p = 0.999) for the "adequate/poor" group. A statistically significant but not clinically relevant worsening of the MDADI-C score was reported for the "optimal" group, whereas both a statistically significant and clinically meaningful improvement of the MDADI-C score were reported for the "adequate/poor" group from before to post-treatment. CONCLUSION: Our results suggest a doubly clinical benefit of dose optimization to SWOARs to minimize the RT sequalae in patients with a baseline "optimal" deglutition-related QoL and to recover from cancer dysphagia in those with a baseline "adequate/poor" deglutition-related QoL.

A Pattern of Care Report on the Management of Patients with Squamous Cell Carcinoma of the Anus-A Study by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gastrointestinal Tumors Study Group.

Background and objectives: The diagnosis and therapy of squamous cell carcinoma of the anus may vary significantly in daily clinical practice, even if international guidelines are available. Materials and Methods: We conducted a pattern of care survey to assess the management of patients with anal cancer in Italy (38 questions). We analyzed 58 questionnaires. Results: Most of the respondents work in public and/or university hospitals (75.8%) in northern Italy (65.5%). The majority (88.0%) treat less than 20 patients/year. Common examinations for diagnosis and staging are anorectal endoscopy (84.5%), computed tomography scan (86.2%) and pelvic magnetic resonance imaging (MRI) (96.5%). The most frequently prescribed dose to primary tumor is 50-54 Gy (46.5-58.6%) for early stage disease and 54-59.4 Gy (62.1-32.8%) for locally advanced cases. Elective volumes are prescribed around 45 Gy (94.8%). Most participants use volumetric intensity modulated radiotherapy (89.7%) and a simultaneous integrated boost (84.5%). Concurrent radiotherapy, 5-fluorouracil and mitomycin is considered the standard of care (70.6%). Capecitabine is less frequently used (34.4%). Induction chemotherapy is an option for extensive localized disease (65.5%). Consolidation chemotherapy is rarely used (18.9%). A response evaluation is conducted at 26-30 weeks (63.9%) with a pelvic MRI (91.4%). Follow-up is generally run by the multidisciplinary tumor board (62.1%). Conclusions: Differences were observed for radiotherapy dose prescription, calling for a consensus to harmonize treatment strategies.

Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs in Anal Cancer Patients Treated with Concurrent Chemo-radiation.

PURPOSE: To investigate whether irradiated volume of pelvic active bone marrow (ACTBM) may predict decreased blood cells nadirs in anal cancer patients undergoing concurrent chemo-radiation. METHODS: Forty-four patients were analyzed and pelvic active bone marrow (ACTBM) was characterized employing 18FDG-PET. Dosimetric parameters on dose-volume histograms were correlated to nadirs with generalized linear modeling. RESULTS: ACTBM mean dose was significantly correlated to white blood cell (ß = -1.338; 95%CI: -2.455/-0.221; p = 0.020), absolute neutrophil count (ß = -1.651; 95%CI: -3.284/-0.183; p = 0.048), and platelets (ß = -0.031; 95%CI: -0.057/-0.004; p = 0.024) nadirs. Other dosimetric parameters were found to be correlated (ACTBM-V10,-V20,-V30and-V40). CONCLUSIONS: 18FDG-PET is able to define active bone marrow and may predict for decreased blood cells count nadirs.

Incorporating 18FDG-PET-defined pelvic active bone marrow in the automatic treatment planning process of anal cancer patients undergoing chemo-radiation.

BACKGROUND: To investigate whether the incorporation of 18FDG-PET into the automatic treatment planning process may be able to decrease the dose to active bone marrow (BM) for locally advanced anal cancer patients undergoing concurrent chemo-radiation (CHT-RT). METHODS: Ten patients with locally advanced anal cancer were selected. Bone marrow within the pelvis was outlined as the whole outer contour of pelvic bones or employing 18FDG-PET to identify active BM within osseous structures. Four treatment planning solutions were employed with different automatic optimization approaches toward bone marrow. Plan A used iliac crests for optimization as per RTOG 05-29 trial; plan B accounted for all pelvic BM as outlined by the outer surface of external osseous structures; plan C took into account both active and inactive BM as defined using 18FDG-PET; plan D accounted only for the active BM subregions outlined with 18FDG-PET. Dose received by active bone marrow within the pelvic (ACTPBM) and in different subregions such as lumbar-sacral (ACTLSBM), iliac (ACTIBM) and lower pelvis (ACTLPBM) bone marrow was analyzed. RESULTS: A significant difference was found for ACTPBM in terms of Dmean (p = 0.014) V20 (p = 0.015), V25 (p = 0.030), V30 (p = 0.020), V35 (p = 0.010) between Plan A and other plans. With respect to specific subsites, a significant difference was found for ACTLSBM in terms of V30 (p = 0.020)), V35 (p = 0.010), V40 (p = 0.050) between Plan A and other solutions. No significant difference was found with respect to the investigated parameters between Plan B,C and D. No significant dosimetric differences were found for ACTLSPBM and ACTIBM and inactive BM subregions within the pelvis between any plan solution. CONCLUSIONS: Accounting for pelvic BM as a whole compared to iliac crests is able to decrease the dose to active bone marrow during the planning process of anal cancer patients treated with intensity-modulated radiotherapy. The same degree of reduction may be achieved optimizing on bone marrow either defined using the outer bone contour or through 18FDG-PET imaging. The subset of patients with a benefit in terms of dose reduction to active BM through the inclusion of 18FDG-PET in the planning process needs further investigation.

Intensity-modulated radiation therapy with simultaneous integrated boost combined with concurrent chemotherapy for the treatment of anal cancer patients: 4-year results of a consecutive case series.

PURPOSE: To report the 4-year outcomes of a consecutive series of anal cancer patients treated with concurrent chemo-radiation delivered with intensity-modulated radiotherapy (IMRT), employing a simultaneous integrated boost (SIB) approach. METHODS: A consecutive series of 54 patients was enrolled between 2007 and 2013. Treatment schedule consisted of 50.4 Gy/28 fractions (1.8 Gy daily) to the gross tumor volume, while the elective nodal volumes were prescribed 42 Gy/28 fractions (1.5 Gy/daily) for patients having a cT2N0 disease. Patients with cT3-T4/N0-N3 tumors were prescribed 54 (T3) or 60 (T4) Gy/30 fractions (1.8-2 Gy daily) to the gross tumor volume; gross nodal volumes were prescribed 50.4 Gy/30 fr (1.68 Gy daily) if sized ≤ 3 cm or 54 Gy/30 fr (1.8 Gy daily) if > 3 cm; elective nodal regions were given 45 Gy/30 fractions (1.5 Gy daily). Chemotherapy was administered concurrently according to the Nigro's regimen. Primary endpoint was colostomy-free survival (CFS). Secondary endpoints were local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and toxicity profile. RESULTS: Median follow up was 32.6 months (range 12-84). The actuarial probability of being alive at 4 years without a colostomy (CFS) was 68.9% (95% CI: 50.3%-84.7%). Actuarial 4-year OS, CSS, DFS, and LC were 77.7% (95% CI: 60.7-88.1%), 81.5% (95% CI: 64%-91%), 65.5% (95% CI: 47.7%-78.5%), and 84.6% (95% CI: 71.6%-92%). Actuarial 4-year metastasis-free survival was 74.4% (95% CI: 55.5%-86.2%). Maximum detected acute toxicities were as follows: dermatologic -G3: 13%; GI-G3: 8%; GU-G3: 2%; anemia-G3: 2%; neutropenia-G3:11%; G4: 2%; thrombocytopenia- G3:2%. Four-year G2 chronic toxicity rates were 2.5% (95% CI: 3.6-16.4) for GU, 14.4% (95% CI: 7.1-28) for GI, 3.9% (95% CI: 1%-14.5%) for skin, and 4.2% (95% CI: 1.1-15.9) for genitalia. CONCLUSIONS: Our study shows the feasibility of IMRT in the combined modality treatment of anal cancer, with comparable results to the literature with respect to LC, sphincter preservation and survival. Acute toxicity is lower if compared to series employing standard techniques. Our results support the use of IMRT on a routine basis for the treatment of anal cancer.

Three-dimensional ultrasound-based image-guided hypofractionated radiotherapy for intermediate-risk prostate cancer: results of a consecutive case series.

External beam radiotherapy (EBRT) is a standard of care in the treatment of prostate cancer. Hypofractionation is a valid option either radiobiologically and logistically in this context. Image-guidance procedures are strongly needed to provide ballistic precision to radiation delivery. The Clarity platform allows for the acquisition of three-dimensional ultrasound scans (3D-US) to perform image-guided radiotherapy. We treated a consecutive series of intermediate-risk prostate cancer patients (according to NCCN stratification) with a hypofractionated schedule (70.2 Gy/26 fractions at 2.7 Gy/daily to the prostate gland excluding the seminal vesicles at 62.1 Gy) under 3D-US guidance with the Clarity platform. The 3-year biochemical-relapse-free survival, distant-metastases-free, cancer-specific and overall survival were 98.6% (CI: 91.1-99.6%), 98.6% (CI: 91.1-99.6%), 97.5% (CI: 94.5-99.1%), and 94.3% (CI: 90.4-96.7%), respectively. Maximum detected acute GU toxicity was G0 in 22 patients (29.7%), G1 in 30 (22.7%), G2 in 19 (25.6%), G3 in 3 (4%). Maximum detected acute GI toxicity at the end of EBRT was G0 in 42 patients (56.8%), G1 in 22 (29.7%), G2 in 9 (12.1%), G3 in 1 (1.4%). The 3-year actuarial rates of ≥ G2 late toxicities were 6.1% for genito-urinary and 8.9% for gastrointestinal. The whole image-guidance workflow resulted in being robust and reliable. EBRT delivered employing a hypofractionated schedule under 3D-US-based image guidance proved to be a safe and effective treatment approach with consistent biochemical control and a mild toxicity profile. Hence, it has been transferred into daily clinical practice in our Department.

Volumetric and positional changes of planning target volumes and organs at risk using computed tomography imaging during intensity-modulated radiation therapy for head-neck cancer: an "old" adaptive radiation therapy approach.

PURPOSE: This study aimed to assess, in a department of radiation oncology not equipped with in-room imaging systems, volumetric and positional changes of planning target volumes (PTVs) and organs at risk in head and neck (H&N) cancer patients treated with intensity-modulated radiation therapy (IMRT), using consecutive off-board computed tomography (CT) imaging. Dosimetric aspects were not investigated. MATERIALS AND METHODS: Ten patients with H&N cancer underwent CT re-scanning at 3, 5, and 7 weeks. Positional changes of the PTVs and parotid glands as distances relative to the virtual isocentre were determined. The parotids glands (PGs) were re-delineated on each CT set and volume differences were computed. Anterior-posterior (AP) and latero-lateral (LL) displacements for the spinal cord at C1 and C6 level were calculated. Changes in patient body contours were evaluated by comparing the volumes within the external skin outline. RESULTS: Apart from two patients requiring re-planning due to substantial weight loss, our results evidenced no significant shifts of PTVs and PGs. PG volume decreased with a trend in volume reduction for the ipsilateral parotid. No significant shift of spinal cord at C1 and C6 level was detected, in either the AP or LL direction. The collected data demonstrated a trend in external skin contour volume loss. CONCLUSIONS: Our preliminary results reflect the literature data and indicate that an off-line adaptive RT approach is appropriate in clinical practice.

Helical tomotherapy and two types of volumetric modulated arc therapy: dosimetric and clinical comparison for several cancer sites.

Radiotherapy accelerators have undergone continuous technological developments. We investigated the differences between Radixact™ and VMAT treatment plans. Sixty patients were included in this study. Dosimetric comparison between the Radixact™ and VMAT plans was performed for six cancer sites: whole-brain, head and neck, lymphoma, lung, prostate, and rectum. The VMAT plans were generated with two Elekta linear accelerators (Synergy® and Versa HD™). The planning target volume (PTV) coverage, organs-at-risk dose constraints, and four dosimetric indexes were considered. The deliverability of the plans was assessed using quality assurance (gamma index evaluation) measurements; clinical judgment was included in the assessment. The mean AAPM TG218 (3%-2 mm, global normalization) gamma index values were 99.4%, 97.8%, and 96.6% for Radixact™, Versa HD™, and Synergy®, respectively. Radixact™ performed better than Versa HD™ in terms of dosimetric indexes, hippocampi D100%, spinal cord Dmax, rectum V38.4  Gy, bladder V30 Gy, and V40 Gy. Versa HD™ saved more of the (lungs-PTV) V5 Gy and (lungs-PTV) Dmean, heart Dmean, breasts V4 Gy, and bowel V45 Gy. Regarding Synergy®, the head and neck Radixact™ plan saved more of the parotid gland, oral cavity, and supraglottic larynx. From a clinical point of view, for the head and neck, prostate, and rectal sites, the Radixact™ and Versa HD™ plans were similar; Radixact™ plans were preferable for the head and neck and rectum to Synergy® plans. The quality of linac plans has improved, and differences with tomotherapy have decreased. However, tomotherapy continues to be an essential add-on in multi-machine departments.

The Prognostic Role of Baseline Eosinophils in HPV-Related Cancers: a Multi-institutional Analysis of Anal SCC and OPC Patients Treated with Radical CT-RT.

BACKGROUND AND AIM: Anal squamous cell carcinoma (SCC) and oropharyngeal cancer (OPC) are rare tumors associated with HPV infection. Bioumoral predictors of response to chemoradiation (CT-RT) are lacking in these settings. With the aim to find new biomarkers, we investigated the role of eosinophils in both HPV-positive anal SCC and HPV-related oropharyngeal cancer (OPC). METHODS: We retrieved clinical and laboratory data of patients with HPV-positive anal SCC treated with CT-RT in 5 institutions, and patients with locally advanced OPC SCC treated with CT-RT in 2 institutions. We examined the association between baseline eosinophil count (the best cutoff has been evaluated by ROC curve analysis: 100 × 10^9/L) and disease-free survival (DFS). Unadjusted and adjusted hazard ratios by baseline characteristics were calculated using the Cox proportional hazards model. RESULTS: Three hundred four patients with HPV-positive anal SCCs and 168 patients with OPCs (122 HPV-positive, 46 HPV-negative diseases) were analyzed. In anal SCC, low eosinophil count (< 100 × 10^9/L) correlates to a better DFS (HR = 0.59; p = 0.0392); likewise, in HPV-positive OPC, low eosinophil count correlates to a better DFS (HR = 0.50; p = 0.0428). In HPV-negative OPC, low eosinophil count confers worse DFS compared to high eosinophil count (HR = 3.53; p = 0.0098). After adjustment for age and sex, eosinophils were confirmed to be independent prognostic factors for DFS (HR = 4.55; p = 0.0139). CONCLUSION: Eosinophil count could be used as a prognostic factor in anal HPV-positive SCC. The worse prognosis showed in HPV-positive patients with high eosinophil count is likely to derive from an unfavorable interaction between the HPV-induced immunomodulation and eosinophils, which may hamper the curative effect of RT.

External validation of a composite bio-humoral index in anal cancer patients undergoing concurrent chemoradiation.

BACKGROUND AND PURPOSE: A prognostic scoring system based on laboratory inflammation parameters, [Hemo-Eosinophils-Inflammation (HEI) index], including baseline hemoglobin level, the systemic inflammatory index and eosinophil count was recently proposed in patients with squamous cell carcinoma of the anus (ASCC). HEI was shown to discriminate disease-free (DFS) and overall (OS) survival in ASCC patients treated with concurrent chemoradiation (CRT). We tested the accuracy of the model on a multicentric cohort for external validation. MATERIALS AND METHODS: Patients treated with CRT were enrolled. The Kaplan-Meier curves for DFS and OS based on HEI risk group were calculated and the log-rank test was used. Cox proportional hazards models were used to assess the prognostic factors for DFS and OS. The exponential of the regression coefficients provided an estimate of the hazard ratio (HR). For model discrimination, we determined Harrell's C-index, Gönen & Heller K Index and the explained variation on the log relative hazard scale. RESULTS: A total of 877 patients was available. Proportional hazards were adjusted for age, gender, tumor-stage, and chemotherapy. Two-year DFS was 77 %(95 %CI:72.0-82.4) and 88.3 %(95 %CI:84.8-92.0 %) in the HEI high- and low- risk groups. Two-year OS was 87.8 %(95 %CI:83.7-92.0) and 94.2 %(95 %CI:91.5-97). Multivariate Cox proportional hazards model showed a HR = 2.02(95 %CI:1.25-3.26; p = 0.004) for the HEI high-risk group with respect to OS and a HR = 1.53(95 %CI:1.04-2.24; p = 0.029) for DFS. Harrel C-indexes were 0.68 and 0.66 in the validation dataset, for OS and DFS. Gonen-Heller K indexes were 0.67 and 0.71, respectively. CONCLUSION: The HEI index proved to be a prognosticator in ASCC patients treated with CRT. Model discrimination in the external validation cohort was acceptable.

Decreasing treatment burden in HPV-related OPSCC: A systematic review of clinical trials.

INTRODUCTION: Favorable outcomes are observed after treatment with standard chemoradiotherapy (CRT) for Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) patients. The consistent growing interest on treatment-related toxicity burden, potentially jeopardizing survivors' quality of life, led clinicians to investigate possible de-escalation strategies. MATERIALS AND METHODS: A comprehensive systematic literature search of clinical trials was performed through the EMBASE database to provide an overview of the de-escalation strategies spectrum. Additionally, hand searching and clinicaltrials.gov were also used. RESULTS: Herein, we report and discuss different approaches to de-escalation of therapy, with respect to both local and systemic strategies. CONCLUSIONS: Several promising de-escalation experiences have been published. However, while further evidence is awaited, no changes in the management nor deviation from the standard of care should be made outside of clinical trials.

Concurrent Chemoradiation in Anal Cancer Patients Delivered with Bone Marrow-Sparing IMRT: Final Results of a Prospective Phase II Trial.

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon's design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; ß = 0.20). A minimum of 21/39 (54%) with G0-G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as 'promising'. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0-G2 HT events were observed, above the threshold set. Hence, 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting.

The Prognostic Value of the New Combined Hemo-Eosinophil Inflammation Index (HEI Index): A Multicenter Analysis of Anal Cancer Patients Treated with Concurrent Chemo-Radiation.

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox's proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04-5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

Radiation therapy for oligometastatic oropharyngeal cancer.

At presentation, isolated metastasis from oropharyngeal squamous cell carcinoma is rare. Liver is a relatively uncommon first site of failure, especially in the absence of other distant metastases, particularly without diagnosis of lung metastases. We report on a case of HPV-related oropharyngeal squamous cell carcinoma with synchronous liver metastasis treated with radiation therapy. This condition, defined as "oligometastatic state," describes a subset of patients with limited volume metastatic disease in whom favorable outcomes were reported with the use of local ablative therapies on both the primary tumor and metastatic sites. As a definitive treatment, we offered the patient, ineligible for other therapeutic approaches, exclusive radiation treatment on the head and neck region and a stereotactic ablative approach targeted to the liver metastasis.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

PURPOSE: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. METHODS: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the ß = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0-G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. RESULTS: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0-G2 events, way above the threshold set by the trial design. CONCLUSION: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

The role of radiotherapy in epithelial ovarian cancer: a literature overview.

Ovarian cancer (OC) accounts for 3% of all cancer in women and for 5% of all cancer-related deaths. Epithelial Ovarian Cancer (EOC) is a radiosensitive malignancy with a poor prognosis. In the pre-chemotherapy era, radiation therapy (RT) delivered to the abdominopelvic region (whole abdominal irradiation, WAI) has historically played a role in the adjuvant and consolidation setting. Specific cluster of patients with early-stage disease and definite histologies may take advantage of RT. Platinum-based chemotherapy (CT) has replaced RT and plays a major role in most of the clinical settings. Radiation Therapy for palliation is recommended in patients with localized symptoms. Nevertheless, modern RT represents a reliable treatment option, with a mild toxicity profile, particularly effective for oligo-recurrent or progressive disease. The present literature review aims to highlight the historical role of RT in EOC, the actual lines of evidence, and the future perspectives.

Radiation-Induced Rhinitis: Cytological and Olfactory Changes.

BACKGROUND: Oral mucositis is a well-known adverse event of radiotherapy (RT) for head and neck cancer (HNC). Its nasal counterpart, the radiation-induced rhinitis, is poorly studied and considered in clinical practice. OBJECTIVE: The aim of this observational study was to evaluate acute cytological and olfactory alterations during RT and their correlation with RT doses. METHODS: Ten patients who underwent RT for HNC, excluding tumors of the nasal cavities, were evaluated with nasal scraping for cytological examination, Sniffin' Sticks test for olfactory assessment, and Nasal Obstruction Symptom Evaluation scale. The examinations were performed before (T0), at mid-course (T1), and at the end (T2) of RT. They were repeated 1 and 3 months after RT (T3 and T4). Mean dose (Dmean) and near maximum dose (D2%) to nasal cavities and inferior turbinates were used for correlation analyses. RESULTS: Radiation-induced rhinitis was present in 70% of patients at T2, and it was still observed in 40% of cases after 3 months. Although olfactory function remained within the normal range at the evaluated times, a significant decrease in odor threshold and discrimination was observed during RT, which returned to baseline levels after RT. Nasal cytology showed a radiation-induced rhinitis with neutrophils and sometimes bacteria. Mucous and squamous cell metaplasia appeared in 10% of patients. Dmean and D2% to inferior turbinates were associated to neutrophilic rhinitis at T2, and D2% to inferior turbinates was correlated to mucous cell metaplasia at T2. CONCLUSIONS: RT for HNC induces acute rhinitis that may persist after the completion of treatment and can affect patient's quality of life. Nasal cytology can help to choose the best treatment on an individual basis.

Prospective assessment of taste impairment and nausea during radiotherapy for head and neck cancer.

Dysgeusia and nausea are common side effects observed in head and neck cancer patients treated with either exclusive radiotherapy or combined modality treatment. The aim of the present study was to prospectively evaluate dysgeusia, during treatment and follow-up, using the chemotherapy-induced taste alteration scale (CiTAS), a metrics based on 18-items exploring three dimensions (quantitative and qualitative changes in taste perception, and diet-related issues) identified through a four-factor analysis: decline in basic taste, discomfort, phantogeusia-parageusia, and general taste alterations. Moreover, we scored, according to Common Toxicity Criteria Adverse Events, nausea and other treatment-related toxicities. Since, ginger is traditionally used to prevent and/or treat nausea and vomiting, we prophylactically employed a ginger-based supplement named Naumix/Naugin (Gamfarma, Milan, Italy), to potentially mitigate both nausea and taste impairment. Using the CiTAS scale, we highlighted a progressive increase in all dysgeusia dimensions, peaking at the VII week of treatment and a subsequent partial late recovery. In particular, we observed a recovery for discomfort, phantogeusia-parageusia, and general taste alterations at 6 months. Grade 2 nausea, observed to be as low as 12.9% potentially due to the use of ginger, peaked at the III week of treatment. Finally, for patients experiencing nausea, the dysgeusia dimension of discomfort was also relevant.

Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier).

Background: In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. Methods: All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. Results: A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (p<0.01) and OS (p=0.046). NLR level was significantly correlated to PFS (p=0.05), but not to OS (p=0.06). PLR level significantly affected both PFS (p<0.01) and OS (p=0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS (p=0.0079), but not to OS (p=0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. Conclusion: The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting.

Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer.

AIM: To report on clinical outcomes of simultaneous integrated boost intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy as per Radiation Therapy Oncology Group (RTOG) 0529 protocol in anal cancer patients. METHODS: Clinical stage T1-T4 N0-N3 anal cancer patients were submitted to concomitant chemoradiation. Patients with cT2N0 disease were prescribed 50.4 Gy/28 fractions to the gross tumor planning target volume (PTV) and 42 Gy/28 fractions to the elective nodal PTV. Patients staged as cT3-T4/N0-N3 were given 54 Gy/30 fractions to the macroscopic anal PTV, while clinical nodes were prescribed 50.4 Gy/30 fractions if <3 cm or 54 Gy/30 fractions if ≥3 cm; elective nodal PTV was prescribed 45 Gy/30 fractions. Two cycles of concomitant 5-fluorouracil and mitomycin C were planned for all patients. Oncological outcomes, acute and late toxicity profiles and pattern of failure were reported. RESULTS: The 3-year colostomy-free survival rate was 64% (95% CI 0.52-0.75). The 3-year local control, disease-free and overall survival rates were 69% (95% CI 0.57-0.79), 71% (95% CI 0.59-0.80) and 79% (95% CI 0.66-0.87), respectively. The cumulative incidence of colostomies was 15.1% (95% CI 8.15-23.88) at 24 months. The cumulative incidence of cancer-specific deaths was 16.4% (95% CI 8.60-26.47) at 36 months. Major acute toxicity consisted of hematological (G3-G4: 26%) and cutaneous (G3-G4: 16%) events. Only one case of ≥G3 late toxicity was documented. CONCLUSIONS: Simultaneous integrated boost IMRT and concurrent chemotherapy as per RTOG 0529 protocol seems to be safe and feasible with consistent oncological outcomes and a mild acute and late toxicity profile in anal cancer patients.