Single Institution Experience in the Management of Locally Advanced (pT4) Differentiated Thyroid Carcinomas.

BACKGROUND: Locally infiltrating (T4) differentiated thyroid carcinomas (DTC) represent a challenge. Surgical strategy and adjuvant therapy should be planned balancing morbidity and oncologic outcome. A series of patients with T4 DTC who underwent multidisciplinary evaluation and treatment is reported. The main study endpoints were the oncologic outcome, complication rates, and risk factors for tumor recurrence. PATIENTS AND METHODS: All DTC cases operated between 2009 and 2021 were reviewed and T4 DTC cases were identified. En bloc resection of inferior laryngeal nerve (ILN), tracheal, and/or internal jugular vein (IJV) was performed in cases of massive infiltration. In cases of pharyngoesophageal junction (PEJ) invasion, the shaving technique was always applied. RESULTS: Among 4775 DTC cases, 60 were T4. ILN infiltration was documented in 45 cases (en bloc resection in 9), tracheal infiltration in 14 (tracheal resection in 2), PEJ invasion in 11 (R0 resection in 7 cases and < 1 cm residual tissue in 4 cases), IJV resection in 6, and laryngeal in 2. In total, 11 postoperative ILN palsy, 23 transient hypoparathyroidisms, and 2 hematomas requiring reoperation were registered. Final histology showed 7 pN0, 22 pN1a, and 31 pN1b tumors. Aggressive variants were observed in 47 patients. All but 1 patient underwent radioiodine treatment, 12 underwent adjuvant external beam radiation therapy (EBRT), and 2 underwent chemotherapy. At a median follow-up of 58 months, no tumor-related death was registered, and seven patients required reoperation for recurrence. Tracheal invasion was the only significant factor negatively impacting recurrence (p = 0.045). CONCLUSIONS: A multidisciplinary approach is essential for the management of T4 DTC. Individualized and balanced surgical strategy and adjuvant treatments, in particular EBRT, ensure control of locally advanced disease with acceptable morbidity.

Can interventional radiotherapy (brachytherapy) be an alternative to surgery in early-stage oral cavity cancer? A systematic review.

PURPOSE: Brachytherapy (BT), also known as interventional radiotherapy (IRT), has proven its utility in the treatment of localized tumors. The aim of this review was to examine the efficacy of modern BT in early-stage oral cavity cancer (OCC) in terms of local control (LC), overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and safety. METHODS: The SPIDER framework was used, with sample (S), phenomena of interest (PI), design (D), evaluation (E), and research type (R) corresponding to early-stage oral cavity cancer (S); BT (PI); named types of qualitative data collection and analysis (D); LC, OS, DFS, CSS, and toxicity (E); qualitative method (R). Systematic research using PubMed and Scopus was performed to identify full articles evaluating the efficacy of BT in patients with early-stage OCC. The studies were identified using medical subject headings (MeSH). We also performed a PubMed search with the keywords "brachytherapy oral cavity cancer, surgery." The search was restricted to the English language. The timeframe 2002-2022 as year of publication was considered. We analyzed clinical studies of patients with OCC treated with BT alone only as full text; conference papers, surveys, letters, editorials, book chapters, and reviews were excluded. RESULTS: The literature search resulted in 517 articles. After the selection process, 7 studies fulfilled the inclusion criteria and were included in this review, totaling 456 patients with early-stage node-negative OCC who were treated with BT alone (304 patients). Five-year LC, DFS, and OS for the BT group were 60-100%, 82-91%, and 50-84%, respectively. CONCLUSION: In conclusion, our review suggests that BT is effective in the treatment of early-stage OCC, particularly for T1N0 of the lip, mobile tongue, and buccal mucosa cancers, with good functional and toxicity profiles.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes.

OBJECTIVE: Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. METHODS: Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. RESULTS: 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/ß10, to the high risk clinical target volume, and 60 Gy EQD2α/ß10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. CONCLUSIONS: In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Treatment of locally advanced and metastatic basosquamous carcinoma, navigating among sonic hedgehog pathway inhibitors, immune checkpoint inhibitors, chemotherapy, and radiotherapy: A case series and literature review.

Locally advanced (laBSCs) and metastatic basosquamous carcinomas (mBSCs) represent a therapeutic challenge. By definition, these forms are not amenable to surgery or radiotherapy, but according to literature reports, sonic hedgehog pathway inhibitors (HHIs), anti-programmed death 1 receptor antibodies (anti-PD-1), and other treatment approaches involving chemotherapy, surgery, and radiotherapy have been used. This work features 5 real-life cases of advanced BSCs, treated at the Dermato-Oncology Unit of Trieste (Maggiore Hospital, University of Trieste). In addition, a review of the current treatment options reported in the literature for laBSC and mBSC is provided, collecting a total of 17 patients. According to these preliminary data, HHIs such as sonidegib and vismodegib could represent a safe and effective first line of treatment, while the anti-PD-1 cemiplimab may be useful as a second-line option. Chemotherapy and combined approaches involving surgery and radiotherapy have been also reported to be suitable in some patients.

Magnetic resonance-guided focused ultrasound versus percutaneous thermal ablation in local control of bone oligometastases: a systematic review and meta-analysis.

BACKGROUND: The percutaneous thermal ablation techniques (pTA) are radiofrequency ablation, cryoablation, and microwave ablation, suitable for the treatment of bone oligometastases. Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive ablation technique. OBJECTIVES: To compare the effectiveness and safety of MRgFUS and pTA for treating bone oligometastases and their complications. METHODS: Studies were selected with a PICO/PRISMA protocol: pTA or MRgFUS in patients with bone oligometastases; non-exclusive curative treatment. Exclusion criteria were: primary bone tumor; concurrent radiation therapy; palliative therapy; and absence of imaging at follow-up. PubMed, BioMed Central, and Scopus were searched. The modified Newcastle-Ottawa Scale assessed articles quality. For each treatment (pTA and MRgFUS), we conducted two separate random-effects meta-analyses to estimate the pooled effectiveness and safety. The effectiveness was assessed by combining the proportions of treated lesions achieving local tumor control (LTC); the safety by combining the complications rates of treated patients. Meta-regression analyses were performed to identify any outcome predictor. RESULTS: A total of 24 articles were included. Pooled LTC rate for MRgFUS was 84% (N = 7, 95% CI 66-97%, I2 = 74.7%) compared to 65% of pTA (N = 17, 95% CI 51-78%, I2 = 89.3%). Pooled complications rate was similar, respectively, 13% (95% CI 1-32%, I2 = 81.0%) for MRgFUS and 12% (95% CI 8-18%, I2 = 39.9%) for pTA, but major complications were recorded with pTA only. The meta-regression analyses, including technique type, study design, tumor, and follow-up, found no significant predictors. DISCUSSION: The effectiveness and safety of the two techniques were found comparable, even though MRgFUS is a noninvasive treatment that did not cause any major complication. Limited data availability on MRgFUS and the lack of direct comparisons with pTA may affect these findings. CONCLUSIONS: MRgFUS can be a valid, safe, and noninvasive treatment for bone oligometastases. Direct comparison studies are needed to confirm its promising benefits.

Definitive chemoradiation in vulvar squamous cell carcinoma: outcome and toxicity from an observational multicenter Italian study on vulvar cancer (OLDLADY 1.1).

BACKGROUND: Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT. METHODS: The primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale. RESULTS: Retrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010-November 2021). Median age at diagnosis was 72 years (range 32-89). With a median follow-up of 19 months (range 1-114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1-53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded. CONCLUSION: In the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management.

Electrochemotherapy with intravenous bleomycin for heavily pre-treated vulvar cancer patients.

OBJECTIVE: The management of vulvar cancer recurrences is complicated by patients' advanced age and comorbidities. Bleomycin-based electrochemotherapy is a potential treatment option in this setting. However, no data on long-term outcomes are available. Therefore, a multicenter observational study was designed to evaluate the 5-year results in these patients. METHODS: Data about patients and tumor characteristics, electrochemotherapy cycles, clinical response, and follow-up were recorded. Treatment procedures were performed according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines. Response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Fifty-one patients (mean age 82.31±7.28 years) with squamous cell vulvar cancer underwent electrochemotherapy (median number of sessions 1; range 1-4). 20 patients had complete response and 32% of these were disease-free after 2 years (median progression-free survival 16.8 months). In 13 patients with partial response the median progression-free survival was 15.36 months, while patients with stable or progressive disease showed tumor relapse after 6.95 and 3.26 months, respectively (p<0.001). Median overall survival was 18.77, 13.07, 6.73, and 11.13 months in patients with complete response, partial response, stable disease, and progressive disease, respectively (p=0.001). CONCLUSION: Long-term follow-up of vulvar cancer patients showed reasonable tumor control after electrochemotherapy and improved progression-free survival and overall survival in responder subjects compared with non-responders. Further studies aimed at improving local response after electrochemotherapy are warranted. Thus, this approach represents a potential alternative for these patients.

Clinical outcomes of teeth adjacent to the site of mandibulotomy or mandibulectomy in patients with head and neck cancer: results from a multidisciplinary mono-institutional head and neck tumor board.

INTRODUCTION: The aim of this case series was to evaluate the necrosis of teeth adjacent to the site of mandibulotomy or mandibulectomy in a cohort of patients suffering from head and neck cancers. METHODS: Fourteen patients who underwent segmental mandibulectomy or paramedian mandibulotomy for oral, oropharynx or major salivary gland cancer and a total of 23 teeth were included in this case series. Twelve patients underwent adjuvant head and neck radiotherapy. Cold sensitivity pulp testing and/or electric pulp testing were performed on teeth at the margin of mandibulectomy and on teeth adjacent to mandibulotomy after surgery. A "positive" response was considered the healthy state, and "negative" was considered the diseased state of the tooth. RESULTS: The 10 patients who underwent mandibulotomy had 12 teeth with a negative response. The 4 patients treated by mandibulectomy had two positive and three negative responses to cold and electric pulp tests. Fifteen out of 23 teeth (65.2%) showed a negative response to sensitivity testing. CONCLUSIONS: Tooth necrosis seems to be a common event after mandibulectomy and mandibulotomy. CLINICAL RELEVANCE: To avoid post-surgery complications, performing root canal therapy before surgery on the teeth adjacent to the surgical site could be an appropriate strategy.

Interventional Radiotherapy (Brachytherapy) in Eyelid and Ocular Surface Tumors: A Review for Treatment of Naïve and Recurrent Malignancies.

The goal of radiotherapy in the treatment of eyelid and ocular surface tumors is to eradicate tumor burden in a manner that maintains visual function and preserve surrounding sensitive ocular tissue. Interventional radiotherapy (IRT-brachytherapy) is a radiotherapy technique associated with a highly focal dose distribution, with the advantage of boosting limited size target volumes to very high dose while sparing normal tissue. The reduction in the ocular and adnexal complications that result from this form of therapy, has led in recent years, to an increase in the use of IRT for the treatment of eyelid and ocular surface tumors. For eyelid malignancies, IRT is used as an independent treatment in small eyelids tumors, in postoperative treatment of high-risk patients and as well as salvage therapy in local recurrences. In the treatment of conjunctival malignancies, due to the high risk of local recurrence, the use of adjuvant therapies as IRT has shown to improve outcomes. In this review, we focus on eyelid and ocular surface IRT techniques and provide an overview of indication, outcomes and toxicity of IRT for the treatment of naïve and recurrent eyelid and conjunctival tumors.

Contact skin radiotherapy (brachytherapy) for the treatment of non-melanoma skin cancers during COVID-19 pandemic.

In the context of the SARS-CoV-2 pandemic, it is important to ensure the quality of cancer treatment as well as patients and health professionals' safety. Individual-based treatment options should be considered in patients with advanced epithelial skin cancer, who are typically elderly and frail. Aim of this study was to assess feasibility and safety of Contact Skin Radiation Therapy (CSRT) to treat basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) during SARS-CoV-2 pandemic. Patients with advanced and difficult-to-treat BCC or SCC were discussed at skin multidisciplinary tumor board (S-MDTB) from February the 21st to May the 4th (phase 1 Italian Pandemic) and retrospectively analyzed. Patient's triage following internal recommendations was daily performed. CSRT was delivered in 8 fractions of 5 Gy each, twice a day. Beyond the clinical outcomes, treatment success indicators, such as the completion of CSRT without SARS-CoV-2 occurrence, were identified to evaluate the feasibility of CSRT during pandemic. A post-treatment psychological assessment regarding patient's safety perception was performed. Six male patients (median age 80 years; range 62-92) with histologically confirmed BCC or SCC were treated with CSRT. Complete clinical remission was achieved in 5/6 patients (83.4%). No high-grade acute toxicities occurred during treatment. No patients or healthcare personnel developed SARS-CoV-2 infection. All the treatment success indicators were achieved. CSRT represents a safe, and feasible treatment option even during the pandemic emergency period. Hypofractionation could be an option to reduce total number of fractions and, consequently, infective risk exposition.

Trans-inguinal pelvic lymphadenectomy in vulvar cancer patients: TRIPLE pilot study.

OBJECTIVE: The goal of this study was to assess the feasibility and safety of a retrograde extraperitoneal trans-inguinal novel approach to pelvic lymphadenectomy in vulvar cancer patients. The secondary objectives were to assess complications (early and late) and oncological outcomes. METHODS: In this pilot study, all patients referred to our institution from November 2019 to May 2021 were evaluated. The inclusion criteria were patients diagnosed with primary/recurrent vulvar cancer and who were candidates for concomitant groin and pelvic lymph node dissection. A consecutive sampling was planned during the study period. After conventional inguino-femoral lymph nodal dissection, ipsilateral extraperitoneal trans-inguinal pelvic lymphadenectomy (TRIPLE) was performed through a groin incision. Clinical data, type of treatment, perioperative complications, and follow-up were evaluated. RESULTS: 13 patients (8 primary, 5 recurrent vulvar cancer) underwent 16 TRIPLE procedures (10 unilateral, 3 bilateral). The median age was 69 years (range 58-93 years); 8 patients had comorbidities (61.5%). Up front locoregional radiotherapy was previously performed in two cases (15.4%). The pathology report showed metastatic lymph nodes in 20 (87%) groins and 11 (68.8%) pelvic sites; the mean number of removed and metastatic pelvic lymph nodes was 12.1 (range 5-33) and 2.9 (range 0-18), respectively. No intra-operative site-specific complications occurred. One (5.9%) post-operative site-specific complication was reported (pelvic abscess, grade 2), which was treated with antibiotics. One patient died due to concomitant pneumonia. No unilateral pelvic lymph node recurrence occurred during follow-up (median 13 months, range 2-43 months); 3 patients (23.1%) had distant site recurrence (median disease-free survival 9 months). CONCLUSIONS: TRIPLE seems to be a feasible and safe technique, providing adequate lymph node dissection. Despite being a high-risk and fragile population, morbidity was similar to previously reported data for conventional mini-invasive approaches. Prospective larger comparative series are necessary.

Clinical impact of SARS-CoV-2 infection among patients with vulvar cancer: the Gemelli Vul.Can multidisciplinary team.

BACKGROUND: 'Severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population. OBJECTIVE: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer. METHODS: Data on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2. RESULTS: One hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35-94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications. CONCLUSIONS: In most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

Multidisciplinary ocular and periocular cancers meetings: implementation in a tertiary referral center and analysis over a 12-months period.

PURPOSE: The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center. METHODS: A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant 'Core team' or - when required - by a broader 'Extended team'. RESULTS: During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%). CONCLUSIONS: Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients.

"Clock mapping" prior to excisional surgery in vulvar Paget's disease: tailoring the surgical plan.

INTRODUCTION: Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. MATERIALS AND METHODS: All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. RESULTS: A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. CONCLUSIONS: Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

Stereotactic radiotherapy (SRT) for differentiated thyroid cancer (DTC) oligometastases: an AIRO (Italian association of radiotherapy and clinical oncology) systematic review.

PURPOSE: The aim of this systematic review was to examine efficacy of stereotactic radiotherapy (SRT) in patients with oligometastatic thyroid cancer. MATERIALS AND METHODS: A systematic search was conducted by means of PubMed, Scopus, and Cochrane library. CLINICALTRIALS: gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical studies as full text carried out on patients with oligometastatic thyroid cancer treated with SRT. Conference papers, surveys, letters, editorials, book chapters, and reviews were excluded. Time of publication was restricted to the years 1990-2021. RESULTS: The number of evaluated patients was 146 (267 lesions), and the median age was 58 years. The median 1-year local control (LC) was 82% (range 67.0%-97.1%); the median disease-free survival (DFS) was 12 months (range 4-53); the median 1-year overall survival was 72% (range 66.6%-85.0%); the 3-year cancer-specific survival was 75.0%; and the 4-year cancer-specific survival was 37.5%. No grade 3-5 acute toxicity was reported. No late effects were recorded. CONCLUSIONS: SRT for oligometastases from thyroid cancer as salvage therapy is well tolerated and yields high rates of LC and prolonged DFS.

Observational multicenter Italian study on vulvar cancer adjuvant radiotherapy (OLDLADY 1.2): a cooperation among AIRO Gyn, MITO and MaNGO groups.

BACKGROUND: Adjuvant radiotherapy (aRT) has been shown to reduce the risk of local relapse in vulvar cancer (VC). In this multicentre study (OLDLADY-1.2), several Institutions have combined their retrospective data on VC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of aRT. METHODS: The primary study end-point was the 2-year-local control, secondary end-points were the 2-year-metastasis free-survival, the 2-year-overall survival and the rate and severity of acute and late toxicities. Participating centres were required to fill data sets including age, stage, tumor diameter, type of surgery, margin status, depth of invasion, histology, grading as well technical/dosimetric details of radiotherapy. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. RESULTS: One hundred eighty-one patients with invasive VC from 9 Institutions were retrospectively identified. The majority of patients were stage III (63%), grade 2 (62.4%) squamous carcinoma (97.2%). Positive nodes were observed in 117 patients (64.6%), moreover tumor diameter > 4 cm, positive/close margins and depth of invasion deeper than 5 mm were found in 59.1%, 38.6%, 58% of patients, respectively. Sixty-one patients (33.7%) received adjuvant chemoradiation, and 120 (66.3%) received radiotherapy alone. aRT was started 3 months after surgery in 50.8% of patients. Prescribed volumes and doses heterogeneity was recorded according to margin status and nodal disease. Overall, 42.5% locoregional recurrences were recorded. With a median follow-up of 27 months (range 1-179), the 2-year actuarial local control rate, metastasis free and overall survival were 68.7%, 84.5%, and 67.5%, respectively. In term of safety, aRT leads to a prevalence of acute skin toxicity with a low incidence of severe toxicities. CONCLUSIONS: In the context of aRT for VC the present study reports a broad spectrum of approaches which would deserve greater standardization in terms of doses, volumes and drugs used.

The role of stereotactic radiotherapy in addition to immunotherapy in the management of melanoma brain metastases: results of a systematic review.

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion. Two studies showed improved overall survival after SRT plus immunotherapy in melanoma cancer patients with brain metastases. Three studies reported data on LC and DFS showing as SRT plus immunotherapy did not improve local control and DFS rates. G3-G4 toxicity was reported in only one study (20% in the SRT plus immunotherapy group versus 23% in the immunotherapy group). Despite SRT plus concurrent immunotherapy seems associated with possible survival advantage and low ≥ G3 late toxicity rates, the quality of evidence is very low. Therefore, in patients with brain metastases from melanoma, SRT plus immunotherapy should be evaluated on an individual basis after discussion by a multidisciplinary team.

EROS 2.0 study: evaluation of two interventional radiotherapy (brachytherapy) schedules for endometrial cancer: a comparison of late vaginal toxicity rates.

BACKGROUND: To compare the late toxicity rates after two different high dose rate (HDR) adjuvant intravaginal interventional radiotherapy (IRT-brachytherapy) dose schedules in stage I-II endometrial cancer. METHODS: Stage I-II patients with endometrial cancer treated with surgery (with or without lymphadenectomy) and adjuvant HDR-IRT between 2014 and 2020 were included in this analysis. Patients were treated with two schedules. In the first cohort (C1), 21 Gy were delivered in three weekly fractions (7 Gy) prescribed 0.5 cm from the applicator surface. In the second cohort (C2), 24 Gy were delivered in four weekly fractions (6 Gy). The clinical target volume was the upper third of the vagina for C1 and the upper 3 cm for C2. HDR-IRT technique and point prescription (5 mm depth from the applicator surface) were the same for all patients. Vaginal toxicity was scored according to the CTCAE 5.0 scale in terms of the presence versus absence of any toxicity grade. The correlation among toxicity and clinical covariates (age, lymphadenectomy, fractionation, stage) was tested by Pearson correlation test (univariate) and by logistic regression (multivariable). RESULTS: 114 stage I and three stage II patients, median age 62 (range: 32-85) years, were included in this analysis. The mean follow-up was 56.3 months in C1 (40-76) and 20 months in C2 (8-42). Vaginal late toxicity was recorded in 40 and 15 patients in C1 and 2, respectively. Age, lymphadenectomy, and fractionation were significantly correlated with toxicity at univariate analysis (p value = 0.029, 0.006, and 0.002, respectively), while stepwise logistic regression confirmed only age and fractionation as significantly correlated parameters (p value = 0.02 and 0.001, respectively). Three-year local relapse-free, distant metastasis-free and cause-specific survival rates were 96.6%, 94.8%, and 99.1%, respectively. CONCLUSIONS: This analysis showed lower vaginal late toxicity rate in C2 compared to C1.

Treatment of Early-Stage Gynecological Cancer-Related Lower Limb Lymphedema by Lymphaticovenular Anastomosis-The Triple Incision Approach.

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs' measures were analyzed by Student's t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA.

Assessment of Sexual Dysfunction in Cervical Cancer Patients after Different Treatment Modality: A Systematic Review.

Background and Objectives: Cervical cancer is a leading cause of mortality among women. Chemo-radiation followed by interventional radiotherapy (IRT) is the standard of care for stage IB-IVA FIGO. Several studies have shown that image-guided adaptive IRT resulted in excellent local and pelvic control, but it is associated with vaginal toxicity and intercourse problems. The purpose of this review is to evaluate the dysfunctions of the sexual sphere in patients with cervical cancer undergoing different cervix cancer treatments. Materials and Methods: We performed a comprehensive literature search using Pub med, Scopus and Cochrane to identify all the full articles evaluating the dysfunctions of the sexual sphere. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results: One thousand three hundred fifty-six women included in five studies published from 2016 to 2022 were analyzed. The median age was 50 years (range 46-56 years). The median follow-up was 12 months (range 0-60). Cervical cancer diagnosis and treatment (radiotherapy, chemotherapy and surgery) negatively affected sexual intercourse. Sexual symptoms such as fibrosis, strictures, decreased elasticity and depth and mucosal atrophy promote sexual dysfunction by causing frigidity, lack of lubrication, arousal, orgasm and libido and dyspareunia. Conclusions: Physical, physiological and social factors all contribute to the modification of the sexual sphere. Cervical cancer survivors who were irradiated have lower sexual and vaginal function than the normal population. Although there are cures for reducing discomfort, effective communication about sexual dysfunctions following treatment is essential.