Prevention and management of radiotherapy-related toxicities in gynecological malignancies. Position paper on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology).

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.

Gastric (gastrointestinal)-type endometrial adenocarcinoma presenting as a solitary endometrial polyp: a case report and literature review on a novel and potentially aggressive endometrial cancer histotype.

Gastric-type carcinoma of the endometrium is a rare endometrial cancer histotype, recently introduced in the 2020 WHO classification of the female genital tract tumors. Clinico-pathological features, as well as treatment strategies for this rare histotype, are not fully defined. We herein present an unusual case of endometrial carcinoma with mucinous features arising in a 58-year-old menopausal woman. Morphological features of the present case as well as immunohistochemical profile were consistent with gastrointestinal differentiation. Therefore, after clinical and imaging studies ruled out the possibility of a metastatic origin, a final diagnosis of gastric-type carcinoma of the endometrium was rendered.

Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival.

PURPOSE: Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. METHODS AND MATERIALS: Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). RESULTS: Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P = .02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P = .02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). CONCLUSIONS: The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Postoperative treatment of intermediate-risk early stage cervical cancer: results of a survey from the Gynecology Study Group in the AIRO Gyn and MITO Groups.

This survey investigated prognostic factors, treatment modalities, references followed and radiation oncologists' opinions to prescribe adjuvant therapy in early intermediate-risk cervical cancer. All but one recommended pelvic radiotherapy ± vaginal boost (45%) with or without chemotherapy (20%). 88% believed other prognostic factors could integrate classic risk criteria. 66% considered chemo-radiation indicated in case of lymphovascular invasion and suboptimal node dissection, high grade, size ≥ 4 cm, non squamous histology and risk factors combination. This wide heterogeneity of treatments reflects the different guideline options due to the lack of defined indications. The need of integrating the classic prognostic factors with others factors was unanimously expressed by radiation oncologists. The best local and systemic therapy should be established through new studies. These results highlighted the need of a position paper to standardize adjuvant treatment in Italy and to design collaborative studies to clarify the controversial aspects.

Healing of a soft tissue wound of the neck and jaw osteoradionecrosis using platelet gel.

AIM: Bone osteoradionecrosis is a serious complication of radiation treatment. Current treatment approaches are not curative and treatment response is often poor leading to high social and healthcare costs. CASE REPORT: We report on the first case of osteoradionecrosis with successful restitutio ab integro by repeated administration of platelet gel (PLT-gel) and surgery in a critically ill patient. The administration of PLT-gel during a severe septic episode helped regeneration of bone and soft tissues, shortening the hospital stay of the patient. It was also noted that following applications of PLT-gel, both the use of morphine and the numbers of infective episodes were reduced. CONCLUSION: Additional studies are needed to confirm the promising effect of PLT-gel for the treatment of osteoradionecrosis.

Localized extranodal lymphoma of the head and neck: retrospective analysis of a series of 107 patients from a single institution.

PURPOSE: To retrospectively analyze the outcome and patterns of relapse in localized extranodal non-Hodgkin's lymphoma of the head and neck (HN-NHL) after radiotherapy alone or combined modality treatment. PATIENTS AND METHODS: A retrospective analysis of 107 patients with HN-NHL was performed. Relapse patterns, overall survival (OS) and relapse-free survival (RFS) were analyzed. Only stage I (n=50) and stage II (n=57) patients were included with either low-grade (n=21) or high-grade (n=86) lymphoma. Fifty-nine patients were treated with radiotherapy (RT) alone and 48 patients received combined-modality treatment (CMT) consisting of chemotherapy (CHOP or CHOP-like) followed by radiotherapy. The volumes of irradiation included local field (n=24), involved field (n=13) and extended field (n=70). The median age at diagnosis was 63 years (range, 17-86 years). RESULTS: The overall response rates (CR+PR) in the radiotherapy group and the combined modality group were 100% and 96%, respectively. With a median follow-up of 49.4 months, 29 of 59 patients after RT alone (37%) and 30 of 48 patients after CMT (62%) were disease-free. In the whole series the projected five-year OS and RFS were 58.7% and 61.8%. At univariate analysis of clinical variables with potential impact on survival including age, stage, histology, IPI score, single or combined treatment and volumes of irradiation, only age and, to a limited extent, type of treatment influenced OS (age < or =60 years 79%, >60 years 41%, P < 0.001; RT alone 54.9%, CMT 62.8%, P = 0.0487) and RFS (< or =60 years 75%, >60 years 50%, P < 0.001; RT alone 54%, CMT 71%, P = 0.039). Better OS and RFS rates were obtained in patients with stage II and high-grade disease treated with CMT (five-year OS and RFS 63% and 69%, respectively; the corresponding values for RT alone were 38% and 34%). The final model of the multivariate analysis retained only age (< or =60 years) as a significant prognostic factor for both RFS and OS (P < 0.001). In the whole series, the sites of relapse were mainly systemic (n = 32/40, 80%) and in-field relapses were rare (n = 3/40, 7.5%). CONCLUSION: HN-NHL is characterized by a high risk of relapse, particularly at distant sites. Older patients have a significantly worse prognosis. Radiotherapy offers a very good local control rate although combined modality treatment possibly produces better RFS and OS, especially for stage II and high-grade disease. Better systemic approaches are warranted for a more consistent impact on survival in this particular subset of extranodal lymphoma. However, radiotherapy alone may offer a feasible and effective modality for patients who cannot tolerate more aggressive treatments. Extended-field radiotherapy and the treatment of a larger number of uninvolved lymph nodal regions does not confer a RFS or OS advantage, either after RT alone or after CMT.

Effectiveness of selective neck dissection in head and neck cancer: the experience of two Italian centers.

OBJECTIVE: The aim of this study was to evaluate the oncologic outcomes after a selective neck dissection (SND), both in elective and therapeutic settings, with particular regard to regional recurrence rate. METHODS: Retrospective analysis of 827 patients with head and neck primary tumors submitted to SND from 1999 to 2011 in two large hospital centers of northern Italy. RESULTS: A total of 40 neck recurrences were found in the whole series, with the same incidence after primary or salvage surgery (4.4% and 5.2%, respectively), but only 22 neck recurrences occurred in the same side of the dissected neck (3.0%). Factors predicting an increase of ipsilateral neck relapse were pathologically positive nodes, number of positive nodes, and nodal ratio (ratio between positive nodes and total nodal removed), but the risk of regional relapse did not exceed 5.0% in any subgroups. A total of 320 patients (39%) had postoperative radiotherapy (52.0% and 22.0% after primary and salvage surgery, respectively). Considering the primary surgery group alone, postoperative radiotherapy produced only a light reduction of homolateral neck recurrence rate in patients with pathological positive nodes (2.4% vs. 5.0%), but it impacted significantly disease-specific survival, both in pathological classification of nodes (pN)1 and pN2-3 patients. CONCLUSION: The SND can be considered a safe and sound procedure both in primary surgery and in salvage setting. Postoperative radiotherapy adds minor advantage to regional control only in node-positive patients but may impact survival. LEVEL OF EVIDENCE: 4.

Determinants of small bowel toxicity in postoperative pelvic irradiation for gynaecological malignancies.

BACKGROUND: Patients treated with postoperative radiotherapy for endometrial and cervical carcinomas from 1981 to 2000 were retrospectively analysed in order to assess the rate of late small bowel toxicity. PATIENTS AND METHODS: Eight hundred and six patients had received pelvic irradiation, with total doses of 40-55 Gy. The mean age was 57 years. Three hundred and eighteen patients had been treated for cervical and 488 for endometrial cancer; 46 had diabetes and 22 vascular diseases; 141 had a history of smoking and 367 were previously submitted to surgery for benign diseases. A CT treatment plan had been applied in 285 patients; 256 had been treated by arc moving therapy, 232 with 2 opposed beams (AP-PA) and 318 with 3 or 4 coplanar beams. Three hundred and forty-six were treated with X photons of 10 MV or more, 202 with 4-5 MV and 258 with cobalt gamma rays. Personalized blocks had been used in 389. Thirty-four women had received chemotherapy. Five hundred and eighty-four had been treated with dose fractions of 180 cGy or more and 56 had received a boost with brachytherapy or external beams. Eighty-one had needed treatment discontinuation due to acute small bowel toxicity. RESULTS: The median follow-up was 70 months. Thirty five patients had bowel obstructions, after a median time of 31 months. The 5- and 10-year toxicity rates were 4 and 7%. Uni- and multivariate comparisons identified age, acute toxicity and dose fraction as predictors for complications. CONCLUSION: Postoperative pelvic irradiation with standard techniques for gynaecological carcinomas results in tolerable rates of clinically significant late bowel damage, while older patients suffering from significant acute toxicity seem to be at higher risk.