Impact of Neoadjuvant Radiochemotherapy on Pathological Complete Response for Locally Advanced Rectal Cancer: A Mono Institutional Experience.

BACKGROUND/AIM: Neoadjuvant radiochemotherapy followed by surgery is a standard of care in locally advanced rectal cancer (LARC). Only a subgroup of patients can obtain a pathological complete response (pCR) and achieve good local control. However, the role of pCR on patient survival is debated. The aim of the study was to evaluate the impact of pCR on clinical outcomes and toxicities in LARC patients treated with dose intensification and concomitant capecitabine treatment in a neoadjuvant radiochemotherapy schedule. PATIENTS AND METHODS: This was a single Institution retrospective study including 178 patients. Mandard tumor regression grade (TRG) and pTNM staging system were used to classify pathological response and define pathological complete response (pCR). Patients were divided in: pCR (pT0N0) and Not-pCR (pT>0N>0), according to pTNM and in good responders (TRG1-2) and partial/not responders (TRG3-5), according to Mandard TRG. The Kaplan-Meier method was used to estimate OS, CSS, DFS and LC. RESULTS: A low severe toxicity rate was observed. Acute Grade 3 lower bowel toxicity and Grade 3 cutaneous toxicity were reported in 2 (1.1%) patients, respectively. Late Grade >3 lower bowel toxicity was reported in 6 patients (3%) and late Grade >3 cutaneous toxicity was registered in one patient. No other severe acute and late toxicities were reported. The 5- and 10-year OS, CSS, DFS and LC rates were 85% and 75%, 94% and 92%, 83% and 81%, 88% and 88%, respectively. We observed a pCR rate of 36% and a good responders rate of 62%, in our study population. Both groups showed better rates for each analyzed clinical outcome. CONCLUSION: Neoadjuvant radiochemotherapy with dose intensification in LARC patients resulted in favorable long-term oncological outcomes, pCR rate showed an optimal impact on OS and DFS with an acceptable toxicity.

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.

Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study.

Treatment response assessment of rectal cancer patients is a critical component of personalized cancer care and it allows to identify suitable candidates for organ-preserving strategies. This pilot study employed a novel multi-omics approach combining MRI-based radiomic features and untargeted metabolomics to infer treatment response at staging. The metabolic signature highlighted how tumor cell viability is predictively down-regulated, while the response to oxidative stress was up-regulated in responder patients, showing significantly reduced oxoproline values at baseline compared to non-responder patients (p-value < 10-4). Tumors with a high degree of texture homogeneity, as assessed by radiomics, were more likely to achieve a major pathological response (p-value < 10-3). A machine learning classifier was implemented to summarize the multi-omics information and discriminate responders and non-responders. Combining all available radiomic and metabolomic features, the classifier delivered an AUC of 0.864 (± 0.083, p-value < 10-3) with a best-point sensitivity of 90.9% and a specificity of 81.8%. Our results suggest that a multi-omics approach, integrating radiomics and metabolomic data, can enhance the predictive value of standard MRI and could help to avoid unnecessary surgical treatments and their associated long-term complications.

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.

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.

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.

Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting.

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making.

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.

BRIDGE -1 TRIAL: BReak Interval Delayed surgery for Gastrointestinal Extraperitoneal rectal cancer, a multicentric phase III randomized trial.

Design: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC).Several studies have shown a correlation between a longer interval between the end of nCRT and surgery (surgical interval - SI) and an increased pathological complete response (pCR) rate, with a maximum obtained between 10 and 13 weeks.The primary endpoint of this multicenter, 2-arm randomised trial is to investigate SI lengthening, evaluating the difference in terms of complete response (CR) and Tumor Regression Grade (TRG)1 rate in the two arms. Secondly, the impact of SI lengthening on survival outcomes and quality of life (QoL) will be investigated. Methods: Intermediate-risk LARC patients undergoing nCRT will be prospectively included in the study. nCRT will be administered with a total dose of 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum of 45 Gy in 25 fractions on the whole pelvis. Chemotherapy with oral capecitabine will be administered continuously.The patients achieving a clinical major or complete response assessed at clinical-instrumental re-evaluation at 7-8 weeks after treatment completion, will be randomized into two groups, to undergo surgery or local excision at 9-11 weeks (control arm) or at 13-16 weeks (experimental arm). Pathological response will be assessed on the surgical specimen using the AJCC TNM v.7 and the TRG according to Mandard. Patients will be followed up to evaluate toxicity and QoL.The promoter center of the trial will conduct the randomization process through an automated procedure to prevent any possible bias.For sample size calculation, using CR difference of 20% as endpoint, 74 patients per arm will be enrolled. Conclusions: The results of this study may prospectively provide a new time frame for the clinical re-evaluation for complete/major responders patients in order to increase the CR rate to nCRT.Trial registration:ClinicalTrials.gov Identifier: NCT03581344.

In-vitro investigation of cardiac implantable electronic device malfunction during and after direct photon exposure: A three-centres experience.

PURPOSE: Radiotherapy may cause malfunction of implantable cardioverter-defibrillators (ICDs) and pacemakers (PMs). We carried-out a multicentre randomized in-vitro study on 65 ICDs and 145 PMs to evaluate malfunctions during and after direct irradiation to doses up to 10 Gy. METHODS: Three centres equipped with different linear accelerator and treatment-planning systems participated in the study. Computed Tomography (CT) acquisitions were performed to build the treatment plans. All devices were exposed to dose of 2, 5, or 10 Gy (6 MV). All devices underwent a baseline examination and 64 wireless real-time telemetry-transmissions (47 ICDs and 17 PMs) were monitored during photon exposures. All devices were interrogated after exposure and once monthly for six subsequent months. RESULTS: Fifty-four of the 64 wireless-enabled CIEDs (84.4%) recorded noise-related interferences during exposure. In detail, 40/47 ICDs (85.1%) reported interference, of which 16 ICDs (34%) reported potentially clinically relevant pacing inhibition and inappropriate detections. Following exposure, a soft reset occurred in 1/145 PM (0.7%) while 7/145 PMs (4.8%) reported battery issues. During the six-month follow-up, 1/145 PM (0.7%) reported a soft reset, while 12/145 more PMs (8.3%) and 1/64 ICD (1.5%) showed abnormal battery depletion. All reported issues occurred independently of exposure dose. Finally, irreversible effects on software and battery life occurred in only non-MRI-compatible devices. CONCLUSION: ICDs mostly featured real-time transient sensing issues, while PMs mostly experienced long-term battery or software issues that were observed immediately following radiation exposure and during follow-up. Irreversible effects on battery life and software occurred in only non-MRI-compatible devices.

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.

Definition of Local Recurrence Site in Resected Pancreatic Adenocarcinoma: A Multicenter Study (DOLORES-1).

The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45-0.53 and 0.58-0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.

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.

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.