Comparative analysis of toxicity in patients with anal cancer undergoing definitive simultaneous integrated boost (SIB) or sequential integrated boost (SeqB) radiotherapy.

PURPOSE: To compare toxicity of radiotherapy (RT) with concomitant chemotherapy (CHT) in patients (pts) with anal cancer treated with simultaneous integrated boost (SIB) versus sequential boost (SeqB). METHODS: Sixty-six patients were treated from 2007 to 2021. Thirty patients underwent to SeqB concurrent to CHT and 37 to SIB-group. Toxicity assessment has been considered in acute and in late toxicities for gastrointestinal (GI), genitourinary (GU), cutaneous (CU) districts, according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. The Wexner scale among summary scoring systems has been used as a tool to measure fecal incontinence. The chi-square test for ordinal variables were used to evaluate the association between patient and treatment characteristics and acute or late severe toxicity. Univariable logistic regression models were fit to evaluate predictive factors associated with fecal incontinence. RESULTS: Median follow-up was 61.5 months (IQR, 27.1-121.7 months) for all patients. Severe acute toxicity (≥ G2) was observed in 49 patients (74.2%). Late toxicity (≥ G2) occurred in 13 cases (19.6%). In assessment of cutaneous toxicity, there was also a significant reduction in ≥ G1 in SIB group with 29 patients (80.5%) vs SeqB group with 29 patients (96.6%) (p-value = 0.046). Of both groups 11 patients (16.6%) developed fecal incontinence, 8 (22%) in the SIB group and 3 (10%) in the SeqB. CONCLUSION: SIB for anal cancer treatment results in reduced acute and late cutaneous toxicity compared to SeqB. According to our results the rate of other acute and late toxicities are low and comparable between the two groups.

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

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

Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcinomas.

OBJECTIVES: To evaluate the efficacy of a second course of fractionated stereotactic radiotherapy (re-SRT) and temozolomide (TMZ) as salvage treatment option in patients with aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs). PATIENTS AND METHODS: Twenty-one patients with recurrent or progressive APTs (n = 17) and PCs (n = 4) who received combined TMZ and re-SRT, 36 Gy/18fractions or 37.5 Gy/15fractions, were retrospectively evaluated. TMZ was given at a dose of 75 mg/m2 given concurrently to re-SRT, and then 150-200 mg/m2/day for 5 days every 4 weeks or 50 mg/m2 daily for 12 months. Local control (LC) and overall survival (OS) were calculated from the time of re-SRT by Kaplan-Meier method. RESULTS: With a median follow-up of 27 months (range 12-58 months), 2-year and 4-year LC rates were 73% and 65%, respectively; 2-year and 4-year survival rates were 82% and 66%, respectively. A complete response was achieved in 2 and partial response in 11 patients. Six patients recurred with a median time to progression of 14 months. O(6)-Methylguanine-DNA methyltransferase (MGMT) status and tumor volume emerged as prognostic factors. Grade 3 radiation-related toxicities occurred in 3 (14%) patients. Grade 2 or 3 hematologic toxicities during chemotherapy occurred in 8 (38%) patients. CONCLUSION: Re-SRT and TMZ is a safe treatment offering high LC in patients with progressive APTs and PCs. The potential advantages of combined chemoradiation as up-front or salvage treatment need to be explored in prospective trials.

Locally advanced inoperable primary or recurrent non-small cell lung cancer treated with 4-week hypofractionated radiation therapy (3 Gy/fraction).

BACKGROUND: The prognosis of locally advanced non-small cell lung cancer (NSCLC) treated with conventional radiotherapy remains poor. Hypofractionation reduces overall treatment time increasing biological effect in patients not suitable for concurrent chemo-radiotherapy. METHOD: From January 2009 to October 2016, 76 inoperable locally advanced primary or recurrent NSCLC patients were treated with 60 Gy in 20 fractions of 3 Gy/each for 4 weeks as exclusive or post-chemotherapy treatment. Fifty-eight patients (76.3%) had stage III and 18 (23.7%) stage IV (≤ 2 metastases) disease: 63 primary (82.9%) and 13 recurrent (17.1%). RESULTS: Median and 2-year overall survival were 17 months and 38.9%, respectively. Median and 2-year loco-regional progression free survival were 27 months and 55.3%, respectively. Univariate and multivariate analyses demonstrated that patients with complete response presented better outcomes, whereas no statistically relevant difference was evidenced in terms of previous chemotherapy, recurrent vs primary disease, volume and stage. Thirty patients (39.5%) presented acute esophagitis (1-grade 3) and 19 (25.0%) acute pneumonitis (2-grade 3). Six patients (7.9%) developed grade 2-3 late pneumonitis and 3 patients (3.9%) grade 1 late esophagitis. CONCLUSION: In patients not suitable of concurrent radio-chemotherapy, exclusive or sequential hypofractionated schedule using 60 Gy in 20 fractions was well tolerated and presented promising results. Complete local response was a predictor of better outcomes, and any efforts will be made to perform prospective clinical trials to further evaluate hypofractionated regimens with increased lesional BED.

Inoperable early-stage primary and early recurrent non-small cell lung cancer: outcomes of a mono-institutional experience using a moderate hypofractionated schedule.

BACKGROUND: Patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) may beneficiate of a hypofractionated radiation therapy in order to intensificate the treatment and to reduce the number of hospital access. METHODS: From 2007 to 2015, 27 patients with early-stage primary or limited loco-regional recurrent (T2a > 4 cm, T2b N0 or T1-2 N1M0) NSCLC were treated. All patients were medically inoperable or refused surgery and were treated with 60 Gy in 20 fractions, 5 times per week. Thirteen (48.1%) presented limited recurrence after surgery and 14 (51.9%) primary disease. RESULTS: Median follow-up was 34 months. Twelve patients achieved a CR (44.4%) and 8 a PR (29.6%) with a tumour response rate of 74%. Median overall survival (OS) and 2-year OS were 34 months and 63.0%, respectively. Median and 2-year loco-regional progression-free survival (LR-PFS) were 31 months and 51.4%, respectively. Survival outcomes were statistically favourable in patients with partial or complete response with respect to patients with stable or progressive disease, whereas stage (N0 vs N1) and primary or relapse/recurrent disease not. No cases of acute toxicity > grade 2 were observed. Seven patients (25.9%) presented grade 2 late toxicities. CONCLUSION: Sixty Gy in 20 fractions is well tolerated and achieves good clinical outcomes in early primary or recurrent NSCLC patients. A greater number of patients and a longer follow-up are necessary to confirm the results obtained with our treatment.

Re-irradiation with curative intent in patients with squamous cell carcinoma of the head and neck: a national survey of usual practice on behalf of the Italian Association of Radiation Oncology (AIRO).

OBJECTIVE: To report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck. METHODS: In March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings. RESULTS: Overall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease. CONCLUSION: Despite the absence of definitive evidence-based recommendations, a possible consideration for ReRT in case of unresectable recurrent head and neck cancer was reported by over 80% of radiation oncologists taking part in the national survey.

Hypofractionated stereotactic radiotherapy in combination with bevacizumab or fotemustine for patients with progressive malignant gliomas.

To evaluate the efficacy of hypofractionated stereotactic radiotherapy performed as reirradiation in combination with fotemustine or bevacizumab as salvage treatment in patients with recurrent malignant glioma. Between May 2006 and December 2013, 54 patients with recurrent malignant glioma received hypofractionated stereotactic radiotherapy (HSRT, 25 Gy in 5-Gy fractions) plus either fotemustine or bevacizumab at University of Rome Sapienza, Sant'Andrea Hospital. All patients had Karnofsky performance score (KPS) ≥ 60 and were previously treated with standard chemoradiotherapy. Forty-two patients had a GBM and 12 patients had an anaplastic astrocytoma (AA). The median overall survival (OS) time and 12-month OS rates after HSRT was 11 months and 30 % for patients treated with HSRT plus bevacizumab and 8.3 months and 5 % for those treated with HSRT plus fotemustine (p = 0.01). Median PFS times were 4 and 6 months for patients treated with HSRT plus fotemustine or bevacizumab, respectively (p = 0.01). KPS > 70 (p = 0.04), AA histology, and the treatment with bevacizumab were independent favourable prognostic factors for OS. In general, both treatments were well tolerated with relatively low treatment-related toxicity. HSRT combined with bevacizumab or fotemustine may represent a feasible treatment option for patients with progressive malignant gliomas, although most of the tumors recur in a few months. Efficacy of bevacizumab or alkylating agents in combination with different radiation schedules needs to be evaluated in prospective studies.

Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers.

Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA.

Fractionated stereotactic radiosurgery for patients with brain metastases.

Stereotactic radiosurgery (SRS) delivered in 2-5 fractions (multi-fraction SRS) has been employed in patients with brain metastases as an alternative to single-fraction SRS with the aim to reduce late radiation-induced toxicity while maintaining high local control rate. In the present study we have evaluated the efficacy and toxicity of multi-fraction SRS in patients with 1-3 brain metastases. Between March 2006 and October 2012, 135 patients (63 men and 72 women) with 171 brain metastases have been treated with multi-fraction SRS (3 × 9 Gy or 3 × 12 Gy). At a median follow-up of 11.4 months, 16 lesions recurred locally. The 1- and 2-year local control rates were 88 and 72 %, respectively. The 1- and 2-year survival rates were 57 and 25 %, and respective distant failure rates were 52 and 73 %. Seventy-eight percent of patients succumbed to their extracranial disease and 22 % died of progressive intracranial disease. Multivariate analysis showed that melanoma histology was predictive of local failure (p = 0.02; HR 6.1, 95 % CI 1.5-24). Specifically, the 1-year local control rates were 68 % for melanoma, 92 % for breast carcinoma, and 88 % for NSCLC, respectively. Stable extracranial disease (p = 0.004) and Karnofsky performance status (p = 0.01) were predictive of longer survival. Radiologic changes suggestive of radionecrosis occurred in 12 (7 %) out of 171 lesions, with an actuarial risk of 9 % at 1 year and 17 % at 2 years, respectively. In conclusion, multi-fraction SRS appears to be an effective and safe treatment modality for brain metastases. It may represent an alternative to single-dose SRS for patients with large lesions or lesions located near critical structures.

Leptomeningeal Carcinomatosis in Early Gastric Cancer: A Case Report and Literature Review.

Leptomeningeal carcinomatosis (LC) is a rare site of metastasis in solid tumors, and it is associated with poor prognosis due to disabling symptoms and a scarcity of treatment options. This condition is an uncommon entity in gastric cancer (GC). We present a case of primary LC manifestation in a patient with an incidental diagnosis of localized node-negative GC. We additionally perform a literature review and discuss the diagnostic and therapeutic challenges. In conclusion, LC from GC represents a rare condition with a dramatic prognosis. Its diagnosis might be very challenging. A multidisciplinary approach appears to be the best strategy for the management of LC from GC.

Re-irradiation for recurrent intracranial meningiomas: Analysis of clinical outcomes and prognostic factors.

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/ß = 2 for brain tissue and α/ß = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

Radiation therapy after breast reconstruction: outcomes, complications, and patient satisfaction.

PURPOSE: The aim of this study was to evaluate treatment-related complications, outcomes, and patient satisfaction in women with locally advanced breast cancer who received post-mastectomy radiation therapy (PMRT) after breast reconstruction (BR). MATERIALS AND METHODS: Between October 2007 and November 2010, 46 patients with locally advanced breast cancer who underwent mastectomy followed by BR received PMRT at our Department. Radiotherapy was delivered to the chest wall with a dose of 50 Gy in 25 fractions over 5 weeks. RESULTS: The median follow-up was 19 months. Skin erythema grade 1 and 2 was seen in 44 (96%) and two (4%) patients, respectively. Major complications, requiring additional corrective surgical procedure, occurred in three (7%) patients (one patient with prosthesis, one patient with tissue expander and one patient with deep inferior epigastric perforator flap). At univariate analysis, smoking, chemotherapy, hormone therapy with tamoxifen and reconstruction with implant were associated with overall complications (capsular contracture and reconstruction failure). Forty (86%) patients were very satisfied or satisfied with the cosmetic outcome of reconstruction. CONCLUSIONS: Radiotherapy can be safely delivered after BR, with a low complication rate and good patient satisfaction. Further randomised studies are needed to better define the optimal timing of breast reconstruction and post-mastectomy radiation therapy.

Clinical Outcomes of Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Patients with Lymph Node Metastases from Gynecological Cancers.

BACKGROUND: To evaluate clinical outcomes of stereotactic body radiation therapy (SBRT) as a local treatment for lymph node metastases from gynecological cancers. METHODS: Between November 2007 and October 2021, we retrospectively analyzed 29 lymph node metastases in 22 oligometastatic/oligoprogressive patients treated with SBRT. The Kaplan-Meier method was used to estimate the rates survival. Univariate analysis for prognostic factors were performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios (HR). RESULTS: Median age was 62 years (IQR, 50-80 years). Median follow-up was 17 months (IQR 10.5-31 months). The median survival was 22 months (CI 95%: 4.2-39.7, IQR: 12.5-34.5 months). Six months, one year and two year overall survival (OS) were 96.6%, 85.2%, and 48.7%, respectively. Median local control (LC) was not reached. Six months, 1one year and 2 year were 93.1%, 87.9%, and 79.9%, respectively. Distant metastasis free survival (DMFS) at one year, and two year was 53% and 37.1%, respectively Four patients (18%) experienced acute G1-G2 toxicities. No G3-4 acute toxicity was reported, and no late toxicity was observed. CONCLUSIONS: SBRT for lymph node recurrence offers excellent in-field tumor control with safe profile and low toxicities. Size, number of oligometastases, and time primary tumor to RT seem to be significant prognostic factors.

Stereotactic body radiation therapy for the treatment of lymph node metastases: a retrospective mono-institutional study in a large cohort of patients.

Introduction: Lymph node metastases (NMs) are a common site of tumor spread that can occur at different times of the disease. Stereotactic body radiation therapy (SBRT) can be a therapeutic option for the treatment of NMs in the setting of oligometastatic disease (OMD). The aim of this study was to evaluate as primary end points the local control (LC) and secondary end points the locoregional nodal control (LRNC), distant nodal control (DNC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), and concurrently to assess the predictive factors of response. Methods: This is a retrospective study that analyzes a group of patients treated with SBRT on NMs from different primary tumors, with a of maximum five metastasis. Treated lesions were divided into four groups: oligometastatics, oligorecurrents, oligoprogressives, and oligopersistents. Results: From 2007 to 2021, 229 NMs were treated in 174 patients with different primary tumor. The schedule most represented was 30 Gy in five fractions. The LC was obtained in 90% of NMs treated by SBRT with rates at 1, 3, and 5 years of 93%, 86%, and 86%, respectively. The LRNC was reached in 84% of cases with rates at 1, 3, and 5 years of 88%, 83%, and 77%, respectively. The DNC was obtained in 87% of cases with rates at 1, 3, and 5 years of 92%, 82%, and 78%, respectively. The DMFS was obtained in 38% of cases with rates at 1, 3, and 5 years of 57%, 40%, and 30%, respectively. The rate of PFS were 44%, 23%, and 13% at 1, 3, and 5 years, respectively. The rates at 1, 3, and 5 years of OS were 78%, 48%, and 36%, respectively. Conclusion: SBRT is an option for the treatment of NMS, with high rates of LC, improving survival, and with a good safety and tolerance. Tumor volume, tumor burden, lesion site, and doses can be predictive factors of response; however, multi-institutional studies with a greater number of patients could be helpful to better select patients and understand the right integrations between ablative treatment and systemic therapies.

Efficacy of Residual Site Radiation Therapy (ISRT) in Patients with Primary Mediastinal Lymphoma with Deauville Score 4 Following R-CHT: Results of a Retrospective Mono Institutional Study.

BACKGROUND: In order to evaluate the efficacy of residual site radiation therapy (RSRT) in terms of progression-free survival (PFS) and overall survival (OS) in patients with primary mediastinal lymphoma (PMBCL) with Deauville Score 4 (DS 4) following rituximab and chemotherapy treatment (R-ICHT). METHODS: Thirty-one patients with PMBCL were recruited. After completion of R-ICHT, patients were staged with 18F-fluorodeoxyglucose positron-emission tomography, showing DS 4, and were treated with adjuvant RSRT. The chosen techniques for RT delivery were intensity-modulated radiation therapy (IMRT) or three-dimensional conformal RT (3D-CRT). Most patients underwent the first one using cone-beam computed tomography (CBCT). All patients were evaluated every 3 months for the first 2 years and every 6 months afterwards for a period of at least 5 years, with clinical and radiological procedures as required. RESULTS: All patients received RSRT with a dose of 30 Gy in 15 fractions. The median follow-up time of 52.7 months (IQR: 26-64.1 months). The 5-year OS rate was 100%. The 2-year and 5-year PFS rates were 96.7% and 92.5%, respectively. Patients with relapsed disease had been treated with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). CONCLUSION: RSRT in patients with PMBCL treated with ICHT and DS 4 did not impact unfavorably on patient survival.

Lymph Node Metastasis in Extraperitoneal Rectal Cancer After Neoadjuvant Therapy: An Unsolved Problem?

BACKGROUND/AIM: Thanks to the promising benefits obtained in terms of quality of life, there has been growing interest in organ-sparing approaches after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer, mainly represented by transanal local excision and watch-and-wait. The main mandatory criterion is complete lymph nodal response (pN0). However, considering the reduced specificity of current radiological means in identifying one-to-one correspondence between clinical and pathological staging, the problem of underestimating lymph nodal involvement remains unsolved. The aim of this study was to identify the true percentage of patients eligible for conservative surgery and possible predictive factors. PATIENTS AND METHODS: Data for 59 patients with rectal cancer treated with nCRT followed by total mesorectal excision were analyzed. Patients with metastatic tumors and tumors treated with up-front surgery were excluded. Our primary endpoint was the pathological lymph nodal response rate after neoadjuvant chemoradiotherapy. The secondary endpoint was to identify predictive factors for lymph nodal response. RESULTS: The percentage of patients with pN0 was 62.71%, while in 37.28%, an organ-sparing approach would have not been oncologically correct. Parameters associated with pN0 were lower tumor size (T0-T2) (p=0.013) and lower grading (

Low Anterior Resection Syndrome (LARS) after Surgery for Rectal Cancer: An Inevitable Price to Pay for Survival, or a Preventable Complication?

BACKGROUND: Rectal cancer is frequent and often treated with sphincter-saving procedures that may cause LARS, a syndrome characterized by symptoms of bowel disfunction that may severely affect quality of life. LARS is common, but its pathogenesis is mostly unknown. The aim of this study is to assess the incidence of LARS and to identify potential risk factors. METHODS: We performed an observational retrospective single center analysis. The following data were collected and analyzed for each patient: demographics, tumor-related data, and intra- and peri-operative data. Statistical analysis was conducted, including descriptive statistics and multivariate logistic regression to identify independent risk factors. RESULTS: Total LARS incidence was 31%. Statistically significant differences were found in tumor distance from anal verge, tumor extension (pT and diameter) and tumor grading (G). Multivariate analysis identified tumor distance from anal verge and tumor extension as an independent predictive factor for both major and total LARS. Adjuvant therapy, although not significant at univariate analysis, was identified as an independent predictive factor. Time to stoma closure within 10 weeks seems to reduce incidence of major LARS. CONCLUSIONS: bold LARS affects a considerable portion of patients. This study identified potential predictive factors that could be useful to identify high risk patients for LARS.

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

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

PERSIAN trial (NCT05717660): an ongoing randomized trial testing androgen deprivation therapy, apalutamide and stereotactic body radiotherapy. An alternative "triplet" for oligometastatic hormone sensitive prostate cancer patients.

Earlier treatment intensification with systemic potent androgen receptor inhibition has been shown to improve clinical outcomes in metastatic hormone sensitive prostate cancer. Nonetheless, oligometastatic patients may benefit from local treatment approaches such as stereotactic body radiotherapy (SBRT). Aiming to explore the benefit of SBRT in this scenario, we designed this trial to specifically test the hypothesis that SBRT will improve clinical outcomes in select population affected by metachronous oligometastatic HSPC treated with androgen deprivation therapy + apalutamide. Enrolled patients will be randomized to receive the standard systemic treatment alone or in combination with SBRT on all metastatic sites of disease. Here we report the protocol design and an overview of the ongoing trials testing different integration strategies between RT and systemic therapies.

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.