Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches.

BACKGROUND: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. METHODS: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. RESULTS: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. CONCLUSIONS: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care.

Preoperative Intensified Chemoradiation with Intensity-Modulated Radiotherapy and Simultaneous Integrated Boost Combined with Capecitabine in Locally Advanced Rectal Cancer: Long-Term Outcomes of a Real-Life Multicenter Study.

BACKGROUND: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. PATIENTS AND METHODS: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. RESULTS: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3-4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3-77.4) and 85.9% (95% CI: 80.2-90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0-13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5-26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3-5 were significantly associated with worse PFS, OS and metastasis-free survival. CONCLUSIONS: Preoperative IMRT-SIB with the moderate dose intensification of 52.5-57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.

Modern Techniques in Re-Irradiation for Locally Recurrent Rectal Cancer: A Systematic Review.

BACKGROUND: Radiotherapy (RT) plays an important role in the treatment of patients with previously irradiated locally recurrent rectal cancer (LRRC). Over the years, numerous technologies and different types of RT have emerged. The aim of our systematic literature review was to determine whether the new techniques have led to improvements in both outcomes and toxicities. METHODS: A computerized search was performed by MEDLINE and the Cochrane database. The studies reported data from patients treated with carbon ion radiotherapy (CIRT), intensity-modulated photon radiotherapy (IMRT), and stereotactic radiotherapy (SBRT). RESULTS: Seven publications of the 126 titles/abstracts that emerged from our search met the inclusion criteria and presented outcomes of 230 patients. OS was reported with rates of 90.0% and 73.0% at 1 and 2 years, respectively; LC was 89.0% and 71.6% at 1 and 2 years after re-RT, respectively. Toxicity data vary widely, with emphasis on acute and chronic gastrointestinal and urogenital toxicity, even with modern techniques. CONCLUSION: data on toxicity and outcomes of re-RT for LRRC with new technologies are promising compared with 3D techniques. Comparative studies are needed to define the best technique, also in relation to the site of recurrence.

Pattern of care for re-irradiation in locally recurrent rectal cancer: a national survey on behalf of the AIRO gastrointestinal tumors study group.

PURPOSE: Radical resection (R0) represents the best curative treatment for local recurrence (LR) rectal cancer. Re-irradiation (re-RT) can increase the rate of R0 resection. Currently, there is a lack of guidelines on Re-RT for LR rectal cancer. The Italian Association of Radiation and clinical oncology for gastrointestinal tumors (AIRO-GI) study group released a national survey to investigate the current clinical practice of external beam radiation therapy in these patients. MATERIAL AND METHODS: In February 2021, the survey was designed and distributed to members of the GI working group. The questionnaire consisted of 40 questions regarding center characteristics, clinical indications, doses, and treatment techniques of re-RT for LR rectal cancer. RESULTS: A total of 37 questionnaires were collected. Re-RT was reported as an option for neoadjuvant treatment in resectable and unresectable disease by 55% and 75% of respondents, respectively. Long-course treatment with 30-40 Gy (1.8-2 Gy/die, 1.2 Gy bid) and hypofractionated regimen of 30-35 Gy in 5 fractions were used in most centers. A total dose of 90-100 Gy as EqD2 dose (α/ß = 5 Gy) was delivered by 46% of the respondents considering the previous treatment. Modern conformal techniques and daily image-guided radiation therapy protocols were used in 94% of centers. CONCLUSION: Our survey showed that re-RT treatment is performed with advanced technology that allow a good management of LR rectal cancer. Significant variations were observed in terms of dose and fractionation, highlighting the need for a consensus on a common treatment strategy that could be validated in prospective studies.

Predictive and prognostic value of inflammatory markers in locally advanced rectal cancer (PILLAR) - A multicentric analysis by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gastrointestinal Study Group.

Background: Patients (pts) affected with locally advanced rectal cancer (LARC) may respond differently to neoadjuvant chemoradiotherapy (nCRT). The identification of reliable biomarkers able to predict oncological outcomes could help in the development of risk-adapted treatment strategies. It has been suggested that inflammation parameters may have a role in predicting tumor response to nCRT and survival outcomes and in rectal cancer, but no definitive conclusion can be drawn at present. The aim of the current study is to evaluate the role of baseline inflammatory markers as prognostic and predictive factors in a large multicentric Italian cohort of LARC pts. Methods: Patients diagnosed with LARC from January 2002 to December 2019 in 9 Italian centers were retrospectively collected. Patients underwent long-course RT with chemotherapy based on fluoropyrimidine ± oxaliplatin followed by surgery. Inflammatory markers were retrieved based on a pre-treatment blood sample including HEI (hemo-eosinophils inflammation index), SII (systemic index of inflammation), NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and MLR (monocyte-to-lymphocyte ratio). Outcomes of interest were pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). Results: 808 pts were analyzed. pCR rate was 22 %, 5yOS and 5yDFS were 84.0% and 63.1% respectively. Multivariate analysis identified that a NLR cut-off value >1.2 and SII cut-off value >500 could predict pCR (p = 0.05 and 0.009 respectively). In addition to age, extramesorectal nodes and RT dose, MLR >0.18 (p = 0.03) and HEI = 3 (p = 0.05) were independent prognostic factors for DFS. Finally, age, RT dose, MLR with a cut-off >0.35 (p = 0.028) and HEI = 3 (p = 0.045) were independent predictors of OS. Conclusions: Higher values of baseline composite inflammatory markers can serve as predictors of lower pCR rates and worse survival outcomes in LARC patients undergoing nCRT. More reliable data from prospective studies could lead to the integration of these inexpensive and easy-to-derive tools into clinical practice.

DWI-MR and PET-CT Functional Imaging for Boost Tumor Volume Delineation in Neoadjuvant Rectal Cancer Treatment.

BACKGROUND/AIM: T2 weighted magnetic resonance (MR) imaging is the gold standard for locally advanced rectal cancer (LARC) staging. The potential benefit of functional imaging, as diffusion-weighted MR (DWI) and positron emission tomography-computed tomography (PET-CT), could be considered for treatment intensification strategies. Dose intensification resulted in better pathological complete response (pCR) rates. This study evaluated the inter-observer agreement between two radiation oncologists, and the difference in gross tumor volume (GTV) delineation in simulation-CT, T2-MR, DWI-MR, and PET-CT in patients with LARC. PATIENTS AND METHODS: Two radiation oncologists prospectively delineated GTVs of 24 patients on simul-CT (CTGTV), T2-weighted MR (T2GTV), echo planar b1000 DWI (DWIGTV) and PET-CT (PETGTV). Observers' agreement was assessed using Dice index. Kruskal-Wallis test assessed differences between methods. RESULTS: Mean CTGTV, T2GTV, DWIGTV, and PETGTV were 41.3±26.9 cc, 25.9±15.2 cc, 21±14.8 cc, and 37.7±27.7 cc for the first observer, and 42.2±27.9 cc, 27.6±16.9 cc, 19.9±14.9cc, and 34.8±24.3 cc for the second observer, respectively. Mean Dice index was 0.85 for CTGTV, 0.84 for T2GTV, 0.82 for DWIGTV, and 0.89 for PETGTV, representative of almost perfect agreement. Kruskal-Wallis test showed a statistically significant difference between methods (p=0.009). Dunn test showed there were differences between DWIGTV vs. PETGTV (p=0.040) and DWIGTV vs. CTGTV (p=0.008). CONCLUSION: DWI resulted in smaller volume delineation compared to CT, T2-MR, and PET-CT functional images. Almost perfect agreements were reported for each imaging modality between two observers. DWI-MR seems to remain the optimal strategy for boost volume delineation for dose escalation in patients with LARC.

Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study.

BACKGROUND: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. METHODS: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. RESULTS: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). CONCLUSIONS: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.

Short course palliative radiotherapy in advanced solid tumors: a pooled analysis (the SHARON project).

Previous trials showed the tolerability and efficacy of a palliative radiotherapy (RT) regimen (SHARON) based on the 4 fractions delivered in 2 days in different oncological settings. In order to identify possible predictors of symptomatic response, the purpose of this study is to perform a pooled analysis of previous trials. We analyzed the impact on symptomatic response of the following parameters: tumor site, histological type, performance status (ECOG), dominant symptom, and RT dose using the Chi-square test and Fisher's exact test. One-hundred-eighty patients were analyzed. Median RT dose was 20 Gy (range: 14-20 Gy). The overall response rate was 88.8% (95% CI 83.3-92.7%) while pre- and post-treatment mean VAS was 5.3 (± 7.7) and 2.2 (± 2.2), respectively (p < 0.001). The overall response rate of pain, dyspnea, bleeding, dysphagia, and other symptoms was 86.2%, 90.9%, 100%, 87.5%, and 100%, respectively. Comparing the symptomatic effect based on the analyzed parameters no significant differences were recorded. However, patients with locally advanced disease showed a higher rate of symptomatic responses than metastatic ones (97.3% vs 83.0%; p = 0.021). Finally, the complete pain response rate was more than double in patients with mild to moderate (VAS: 4-7) compared to those with severe (VAS > 7) pain (36.0% vs 14.3%; p = 0.028). This pooled analysis showed high efficacy of the SHARON regimen in the relief of several cancer-related symptoms. The markedly and significantly higher complete pain response rate, in patients with mild-moderate pain, suggests early referral to palliative RT for patients with cancer-related pain.

Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise).

Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP­cancer pain, NCP­non-cancer pain, MP­mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7−10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.

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.

Smile InTM Totems in Radiotherapy: Patients' Satisfaction with Limited Equipment and COVID-19.

BACKGROUND: We report a mono-institutional experience regarding patient-perceived quality regarding the Chieti Radiotherapy Department, through RAMSI (Radiotherapy Amica Mia-SmileINTM(SI)-My Friend RadiotherapySI) project, in critical scenarios of limited equipment and COVID-19. MATERIAL AND METHODS: Patient-reported experience measures (PREMs) were assessed as follows: Patient-centric welcome perception (PCWP), Comfort, Professional skills and Punctuality. Patients could give anonymous feedback using HappyOrNot technology through four totems located in strategic areas within the center. An internal benchmark was obtained using the feedback received after a preliminary observation period. The SI Experience Index was collected, analyzed and compared. Weekly and monthly reports were generated. RESULTS: From February 2019 to February 2022, 8924 patients accessed the department; 17,464 daily treatments were recorded and 5830 points of feedback were collected: 896, 1267, 1125 and 2542 for PCWP, Comfort, Professional skills and Punctuality, respectively. A LINAC decommissioning period was analyzed, with decreases in the SI-Index score and Smile-IN approved percentage and an improvement after this period. Additionally, the COVID-19 pandemic was analyzed with a mild evaluations decrease for PREM's Welcome, Comfort and Punctuality (Δ-value: -9%, -3% and -4%, respectively), while Professional skills were always optimal. CONCLUSION: The RAMSI project was effective for assessing treatment quality perception, allowing for improving clinical procedures with corrective actions. The RAMSI project is ongoing.

Whole breast radiotherapy in cN0 early breast cancer patients with pathological sentinel lymph nodes (pN1mic, pN1a) without axillary dissection: preliminary results of the observational LISEN trial.

PURPOSE: Axillary management remains unclear when sentinel lymph node (SLN) results are positive in cN0 patients with breast cancer (BC). The trial ACOSOG Z0011 represented a revolution with axillary lymph node dissection (ALND) omission in SLN+ patients, despite critiques regarding non-uniformity of radiation fields. We conducted an observational study (LISEN) where whole breast radiotherapy (WBRT) was planned with tangential fields without nodal irradiation in patients eligible for the Z0011 trial. METHODS: Inclusion criteria were female patients with histologically proven BC, cT1-2cN0, planned conservative surgery, no neoadjuvant therapy. Patients were stratified into two groups: micrometastatic (pN1mic, group 1) and macrometastatic (pN1a, group 2) lymph nodes. Tangential field WBRT was mandatory. Clinical outcomes were analysed, measured from surgery until the first event. RESULTS: In all, 199 patients underwent conservative surgery and SLN biopsy; 133 patients meeting criteria were analysed: 41 patients (30.8%) pN1mic and 92 (69.2%) pN1a. The 5­year disease-free survival (DFS) was 95.0% (85.9-100%) in group 1 and 93.0% (86.3-100.0%) in group 2 (p = 0.78). Overall survival (OS) was 100% (100-100%) in group 1 and 97.4% (92.4-100%) in group 2 (p = 0.74). For the whole cohort DFS and OS were 93.6% (88.2-99.4%) and 96.9% (91.5-100.0%), respectively. For groups 1 and 2, the 5­year outcomes were 5.0% (0.0-14.4%) and 2.3% (0.0-6.1%) for local recurrence (p = 0.51), and 6.2% (0.0-17.4%) and 7.0% (0.0-13.7%) for distant metastasis (p = 0.61), respectively. In group 1, regional recurrence (RR) and local regional recurrence (LRR) were 5.0% (0.0-14.1%; p = 0.13). In group 2, RR and LRR were 0.0% (0.0-0.0%). CONCLUSION: Our results showed good regional control in patients who met the Z0011 trial criteria. WBRT, without nodal surgery or RT, avoiding axillary morbidity, seems to be a good choice.

Lower Bladder Toxicity of Salvage Versus Adjuvant Modern Radiotherapy for Prostate Cancer Patients.

BACKGROUND/AIM: In prostate cancer, postoperative radiotherapy timing is debated to avoid overtreatments and toxicities. This study compared acute and late rectal and bladder toxicities in the adjuvant and salvage setting. PATIENTS AND METHODS: In total, 129 patients were analyzed in two groups: adjuvant radiotherapy (aRT) and salvage radiotherapy (sRT). RESULTS: In aRT and sRT, grade 1 (G1) acute bladder toxicities were detected in 40 and 30 patients, and grade 2 (G2) in 1 and 6; G1 late bladder toxicities were described in 30 and 20, and G2 in 6 and 2, respectively. In aRT and sRT, acute G1 rectal toxicities were reported in 18 and 27 patients, and G2 in 5 and 4, respectively. Late rectal G1 toxicities were observed in 10 patients, G2 in 6 and G3 in 1 in the aRT. In sRT, 8 patients and 1 developed G1 and G2 toxicities, respectively. Regarding bladder toxicity, a higher incidence occurred in aRT; late toxicity was lower in sRT. CONCLUSION: Adjuvant and salvage RT in prostate cancer treatment resulted in acceptable toxicities.

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.

Treatment Volume, Dose Prescription and Delivery Techniques for Dose-intensification in Rectal Cancer: A National Survey.

BACKGROUND/AIM: The aim of the study was to investigate boost volume definition, doses, and delivery techniques for rectal cancer dose intensification. PATIENTS AND METHODS: An online survey was made on 25 items (characteristics, simulation, imaging, volumes, doses, planning and treatment). RESULTS: Thirty-eight radiation oncologists joined the study. Twenty-one delivered long-course radiotherapy with dose intensification. Boost volume was delineated on diagnostic magnetic resonance imaging (MRI) in 18 centres (85.7%), and computed tomography (CT) and/or positron emission tomography-CT in 9 (42.8%); 16 centres (76.2%) performed co-registration with CT-simulation. Boost dose was delivered on gross tumor volume in 10 centres (47.6%) and on clinical target volume in 11 (52.4%). The most common total dose was 54-55 Gy (71.4%), with moderate hypofractionation (85.7%). Intensity-modulated radiotherapy (IMRT) was used in all centres, with simultaneous integrated boost in 17 (80.8%) and image-guidance in 18 (85.7%). CONCLUSION: A high quality of treatment using dose escalation can be inferred by widespread multidisciplinary discussion, MRI-based treatment volume delineation, and radiation delivery relying on IMRT with accurate image-guided radiation therapy protocols.

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4-87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1-79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8-89.4) (95% CI: 78.5-81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Quality of Life in Early Breast Cancer Patients: A Prospective Observational Study Using the FACT-B Questionnaire.

BACKGROUND/AIM: Quality of life (QoL) in early breast cancer (BC) treatment may be affected by acute and late toxicities. This study evaluated the impact of radiotherapy (RT) schedules, treatment-related toxicities, hormone therapy (HT) and age on QoL. PATIENTS AND METHODS: Ninety-five patients answered the FACT-B 4.0 questionnaire. Acute or late toxicities were recorded at each follow-up visit. RESULTS: The median trend of the QoL subscales was stable during all questionnaires. HT negatively impacted on Functional Assessment of Cancer Therapy-General-Total, functional and emotional wellbeing. No difference was recorded between RT schedules and toxicity. No significant differences for age were detected in QoL. CONCLUSION: RT seems not to influence QoL of BC patients, in terms of fractionation regimen or RT-related side-effects. Moreover, women having systemic HT experienced a QoL worse than patients treated with RT only. Further and long-term protocols are needed to improve the validity of the tool.

Outcomes and toxicities of re-irradiation for prostate cancer: A systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

AIMS: The best therapeutic approach for local relapses of previously irradiated prostate cancer (PC) is still not defined. Re-irradiation (Re-I) could offer a chance of cure for highly selected patients, although high quality evidences are lacking. The aim of our study is to provide a literature review on efficacy and safety of Re-I. METHODS: Only studies where Re-I field overlaps with previous radiotherapy were considered. To determine 2 and 4 years overall mortality (OM), 2 and 4 years biochemical failure (BF) and pooled acute and late G ≥ 3 toxicities rate, a meta-analysis over single arm study was performed. RESULTS: Thirty-eight studies with 1194 patients were included. Median follow-up from Re-I was 30 months (10-94 months). Brachytherapy (BRT) was the most used Re-I technique (27 studies), followed by Stereotactic Body Radiotherapy (SBRT) (9) and External Beam Radiation Therapy (EBRT) (2). Re-I prescription doses ranged from 19 Gy in single HDR fraction to 145 Gy (interstitial BRT). The pooled 2 and 4 years OM rates were 2.1% (95%CI:1.1-3.7%, P < 0.001) and 12.5% (95%CI:8.1-19.5%; P < 0.001). The pooled 2 years BF rate was 24% (95% CI: 19.1-30.2%, P < 0.001). The pooled 4 years BF was 35.6% (95% CI: 28.7-44.3%, P < 0.001). The pooled result of G ≥ 3 acute toxicity was 1.4% (95%CI: 0.7-3%, P < 0.001). One hundred and three G ≥ 3 late adverse events were reported, with a pooled result of G ≥ 3 late toxicity of 8.7% (95%CI: 5.8-13%, P < 0.001). CONCLUSIONS: Re-I of local failures from PC showed promising OM and biochemical control rates with a safe toxicity profile.

Cumulative dose, toxicity, and outcomes of spinal metastases re-irradiation : Systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: The aim of this study was to identify patient-, tumor-, or treatment-related factors which may affect disease-related outcomes of re-irradiation (reRT) in patients with previously irradiated vertebral metastases. METHODS: A computerized search of the literature was performed by searching for terms related to reRT and spinal metastases in MEDLINE, EMBASE, OVID, and the Cochrane database from 1995 to 2019. Studies including at least 10 patients who had received reRT at the same site of initial radiotherapy for vertebral metastases with localized external beam radiotherapy were included. To determine the pooled ≥G3 acute and late toxicity rate, pain relief, local control, and overall survival, a meta-analysis technique of single-arm studies was performed. RESULTS: Nineteen studies including 1373 patients met the inclusion criteria for this systematic review. The pooled pain relief, neurological improvement, 1­year local control, and 1­year overall survival rates were 74.3%, 73.8%, 78.8%, and 54.6%, respectively, with moderate to high heterogeneity among studies. No difference in heterogeneity was evidenced for pain relief or local control after omitting studies not using stereotactic body radiotherapy (SBRT) or studies delivering biologically effective dose (BED) < 45 Gy10, whereas heterogeneity for 1­year OS was lower after omitting studies not using SBRT and delivering BED < 45 Gy10. The pooled results of grade ≥ 3 acute and late toxicity were 0.4% (95% confidence interval: 0.1-1.2%) and 2.2% (95% confidence interval: 1.2-37%), respectively, with low heterogeneity among studies. CONCLUSION: While this systematic review confirmed that reRT is both safe and effective for treating patients with recurrent spinal metastases, it could not identify factors which may affect outcomes of reRT in this patient population.

Multimodal Evaluation of Voice Outcome in Early Glottic Cancers Treated With Definitive Radiotherapy.

Background/Aim: We employed a multimodal evaluation of voice outcome (MEVO) model to assess long-term voice outcome in early glottic cancer (EGC) patients treated with primary radiotherapy (RT). The model consisted of objective and subjective vocal evaluation during follow-up, by a dedicated Speech Pathologist and Speech Therapist. Patients and Methods: MEVO methodology includes Self-perception Voice Handicap Index (VHI-30), evaluation of parameters Grade (G), Roughness (R), Breathiness (B), Asthenia (A) and Strain (S) according to GRBAS scale, objective analysis and aerodynamics using the PRAAT software and laryngeal evaluation with videostroboscope (VS). Results: The MEVO methodology was described and tested on a sample of 10 EGCs submitted to definitive RT (total dose 66-70 Gy). Mean follow-up was 48.9 months (range=9-115). VHI was mild-moderate in 90% of patients; overall voice function (GRBAS) was normal-mildly impaired in 70% of patients; VS evaluation showed normal vocal cord motion in 90% of patients, but complete glottic closure in 60%. PRAAT scores confirmed these findings. Conclusion: A multidimensional voice evaluation is time consuming, but useful to objectify vocal impact of radiotherapy. The MEVO model allowed to quantify vocal dysfunction, showing a good objective vocal outcome.