Definitive radiotherapy for recurrent vulvar carcinoma after primary surgery: a two-institutional Italian experience.

OBJECTIVE: To assess the clinical outcome of patients treated with radiotherapy (RT) for recurrent squamous cell carcinoma of the vulva after primary surgery. METHODS: Fifty-six patients developed recurrent disease after surgery, consisting of deep total vulvectomy with inguino-femoral lymphadenectomy in 44 (78.6%) and deep partial vulvectomy with inguino-femoral lymphadenectomy in 12 (21.4%). All patients underwent RT at the Divisions of Radiotherapy, University of Pisa and ASST Cremona, between 1992 and 2016. Forty-three patients (76.8%) underwent external beam RT and 13 (23.2%) were treated with exclusive high-dose rate brachytherapy. RESULTS: Five-year progression-free survival (PFS) and overall survival (OS) were 19% and 43%, respectively. Primary tumor size ⩽4 cm, early FIGO stage, and negative lymph node status were significantly associated with better PFS (p = .005, p = .020 and p = .036, respectively) and OS (p < .0001, p = .023 and p = .008, respectively). Patients with more than 1 positive lymph node at primary surgery had significantly worse PFS (p = .028) and OS (p = .001). Patients with local recurrence had significantly better PFS and OS (p = .022, p = .002, respectively). RT total dose >54 Gy was associated with a lower risk of recurrence. CONCLUSIONS: Primary tumor size, FIGO stage, nodal status, and site of recurrent disease were significant predictors of clinical outcome in patients treated with RT for recurrent squamous cell carcinoma of the vulva.

Adjuvant Radiotherapy in High-Risk Squamous Cell Carcinoma of the Vulva: A Two-Institutional Italian Experience.

BACKGROUND: The aim of this study was to assess the treatment benefit and patterns of recurrence for patients with high-risk vulvar squamous cell carcinoma treated with surgery followed by adjuvant radiotherapy (RT). PATIENTS AND METHODS: From January 1999 to June 2016, 51 patients underwent total or partial deep vulvectomy with inguinofemoral lymphadenectomy followed by adjuvant RT with 45-50 Gy in 25 fractions +/- a 4-10 Gy boost. 17 (33.3%) women received concomitant chemotherapy. RESULTS: Median overall survival was 81 months. The 5-year disease-free survival and overall survival rates were 52 and 63%, respectively. In univariate and multivariate analysis, patients aged ≤ 76 years and those receiving an RT total dose of > 54 Gy had a significantly lower risk of progression (p = 0.044 and 0.045; p = 0.012 and 0.018, respectively) and death (p = 0.015 and 0.011; p = 0.015 and 0.026, respectively). There was a trend towards a lower risk of progression for patients with tumor size ≤ 4 (p = 0.098) and negative lymphovascular space involvement (p = 0.080). Also, there was a trend towards a higher risk of death (p = 0.075) for grade 3 tumors. Concomitant chemotherapy provided no significant benefit. CONCLUSION: Only age and RT total dose are significant prognostic variables for squamous cell carcinoma of the vulva treated with primary surgery and adjuvant RT to improve local and locoregional control.

Definitive Radiotherapy for Primary Squamous Cell Carcinoma of the Vagina: Are High-Dose External Beam Radiotherapy and High-Dose-Rate Brachytherapy Boost the Best Treatment? Experience of Two Italian Institutes.

INTRODUCTION: We assessed the clinical outcome and survival of 70 patients with primary vaginal squamous cell carcinoma undergoing radiotherapy (RT) at the Divisions of Radiotherapy, University of Pisa and ASST Cremona between January 1995 and June 2016. METHODS: 58 patients received external beam RT (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose: 45-50.4 Gy). 29 patients (41.4%) received concomitant weekly cisplatin 40 mg/m2. 35 patients received an additional (15-36 Gy) high-dose-rate (HDR) brachytherapy (BT) boost and 13 received an additional (9-25 Gy) EBRT boost to the primary tumor site. 12 women exclusively received HDR-BT up to a total dose of (30-58 Gy). RESULTS: Median overall survival (OS) was 85 months. A total RT dose of > 60 Gy was significantly associated with a better OS (p = 0.015). There was a trend for a better OS for patients aged < 70 years and for those undergoing EBRT to the entire vagina and pelvis plus BT boost. The most common grade 1-2 acute toxicities were diarrhea (24.1%) and cystitis (20.7%); grade 3 cystitis only occurred in 2 patients (3.4%). CONCLUSIONS: EBRT followed by BT boost seems to be the best treatment for vaginal carcinoma. The total dose of RT should be > 60 Gy.

Neoadjuvant chemotherapy and radical radiotherapy associated with cetuximab for laryngeal cancer in a pancreas and renal recipient.

The oncological treatment for advanced stage head and neck cancer is based on a combination of cisplatin and cetuximab, and radiotherapy. However, very few data are available on this multimodal approach for this type of cancer in pancreas and renal recipients. We report the case of a pancreas and renal recipient being treated with combined chemoradiotherapy for a locally advanced squamous cancer of the larynx. The patient was under treatment with ciclosporin-based immunosuppressive therapy at the time of cancer diagnosis, which was then replaced by everolimus. After 4 years of follow-up, the patients is still free from disease, with a local complete response, only mild residual dysphonia, and with edema of the chin. Cetuximab plus radiation could be an adequate option for cancer treatment in solid organ transplant recipients affected by locally advanced head and neck cancer; the concomitant use of mammalian target of rapamycin pathway inhibitors may have a synergistic effect in enhancing tumor control in these patients; however, further dedicated studies are warranted.

Brachytherapy in non melanoma skin cancer of eyelid: a systematic review.

PURPOSE: Non melanoma skin cancers (NMSC) of eyelid are uncommon. Many treatments approach are available with surgery being considered as the gold standard. Radiotherapy is an effective alternative in patients unfit for surgery. Brachytherapy (BT) might be a better therapeutic option due high radiation dose concentration to the tumor and rapid dose fall-off resulting in normal tissues sparing. The aim of this review is to evaluate local control, toxicity, and functional cosmetic outcome of BT in NMSC of eyelid. MATERIAL AND METHODS: A systematic search of the bibliographic databases PubMed, Scopus, and Cochrane Library from the earliest possible date through October 2015 was performed. Only studies published in English were included. RESULTS: Six articles fulfilled the selection criteria and were included in our review. Due to high risk of bias, all studies were classified to provide a low level of evidence (according to Scottish Intercollegiate Guidelines Network Classification). No randomized controlled trials or case control studies were founded. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 95.2%). Functional and cosmetic outcome were reported in five study as acceptable good functional-cosmetic outcome (median: 100%). CONCLUSIONS: To date, few evidences are available on the role of BT in eyelid NMSC, and they show satisfactory results in terms of local control and functional cosmetic outcome. Therefore, prospective controlled trials are justified.

Merkel cell carcinoma: a retrospective study on 48 cases and review of literature.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Fourty-eight patients with MCC were observed at the Rare Hormonal Tumors Group of Cremona Hospital, 15 of these with unknown primary site. Due to rarity of Merkel cell carcinoma, clinical experience is generally limited. Data from our series confirm the current recommendations. Wide surgical excision must be associated with radiotherapy also in early stages in order to avoid local relapse and the rapid progression of disease. In advanced stages chemotherapy is the standard despite the short duration of responses and poor quality of life. The data of our series, characterized by a high demand for second opinion, offer some insight about the real rarity of the tumor, the difficulty of managing of disease in our country secondary to a wrong cultural approach to the problem, the indiscriminate use of molecules unnecessary and often expensive, the lack of protocols, and the presence of guidelines often ignored. This results in very poor survival associated with a very low quality of life, requiring to find the right direction towards a correct management of disease.

Cranio-spinal irradiation with volumetric modulated arc therapy: a multi-institutional treatment experience.

PURPOSE: To report the treatment of cranio-spinal irradiation (CSI) with volumetric modulated arc therapy (RapidArc) in adults and a child. MATERIALS AND METHODS: Five patients from 5 institutions were treated with CSI using RapidArc technology. Patient age varied between 7 and 45 years. The lengths of the planning target volumes (PTV) and dose prescriptions ranged from 54.6 to 78.4 cm, and from 12 to 36 Gy, respectively. Different arc arrangements were used, with two or three isocentres, from two to six modulated arcs, for patient positioned either in prone (n=3) or supine position (n=2). Doses to PTV, organs at risk and non-target tissue are reported for each of the five patients. Data concerning imaging strategy and pre-treatment quality assurance are also reported. RESULTS: The mean conformity index CI(95%) was 1.05 ± 0.05 (range: 1.00, 1.13). Mean doses to the lenses, lungs, heart, and kidneys were, respectively, 7.6 ± 1.6, 6.6 ± 3.0, 5.7 ± 2.3, and 6.1 ± 2.1 Gy, keeping those value acceptably low. Mean non-target tissue dose was 21.0 ± 3.8% (5.6 ± 1.8 Gy, range: 3.0-8.1 Gy). All patients were successfully planned and treated with RapidArc. CONCLUSIONS: RapidArc techniques achieved highly conformal treatment plans for 5 adults or paediatric patients. Beam-on time was short, and RapidArc plans were satisfactorily delivered to all presented patients.

Impact of radiotherapy technique on the outcome of early breast cancer treated with conservative surgery: A multicenter observational study on 1,176 patients.

PURPOSE: To quantify the impact of radiotherapy technique on cosmetic outcome and on 5-year local control rate of early breast cancer treated with conservative surgery and adjuvant radiation. METHODS AND MATERIALS: A total of 1,176 patients irradiated to the breast in 1997 were entered by eight centers into a prospective, observational study. Surgical procedure was quadrantectomy in 97% of patients, with axillary dissection performed in 96%; pT-stage was T1 in 81% and T2 in 19% of cases; pN-stage was N0 in 71%, N + (1-3) in 21%, and N + (>3) in 8% of cases. An immobilization device was used in 17% of patients; external contour-based and computed tomography-based treatment planning were performed in 20% and 72% of cases, respectively; 37% of patients were treated with a telecobalt unit and 63% with a linear accelerator; portal verification was used in 55% of patients; a boost dose to the tumor bed was delivered in 60% of cases. RESULTS: With a median follow-up of 6.2 years, local, regional, and distant control rates at 5 years are 98%, 99%, and 92%, respectively. Use of less sophisticated treatment technique was associated with a less favorable cosmetic outcome. Local control was comparable between centers despite substantial technical differences. In a multivariate analysis including clinical and technical factors, only older age and prescription of medical adjuvant treatment significantly predicted for better local control, whereas use of portal verification was of borderline significance. CONCLUSIONS: Radiation technical factors impacted negatively on cosmetic outcome, but had relatively small effects on local control compared with other clinical factors.

Patterns of practice and survival in a retrospective analysis of 1722 adult astrocytoma patients treated between 1985 and 2001 in 12 Italian radiation oncology centers.

PURPOSE: To analyze the patterns of practice and survival in a series of 1722 adult astrocytoma patients treated in 12 Italian radiotherapy centers. METHODS AND MATERIALS: A total of 1722 patients were treated with postoperative radiotherapy (90% World Health Organization [WHO] Grade 3-4, 62% male, 44% aged >60 years, 25% with severe neurologic deficits, 44% after gross total resection, 52% with high-dose radiotherapy, and 16% with chemotherapy). Variations in the clinical-therapeutic features in three subsequent periods (1985 through 2001) were evaluated, along with overall survival for the different subgroups. RESULTS: The proportion of women, of older patients, of those with worse neurologic performance status (NPS), with WHO Grade 4, and with smaller tumors increased with time, as did the proportion of those treated with radical surgery, hypofractionated radiotherapy, and more sophisticated radiotherapy techniques, after staging procedures progressively became more accurate. The main prognostic factors for overall survival were age, sex, neurologic performance status, WHO grade, extent of surgery, and radiation dose. CONCLUSIONS: Recently, broader selection criteria for radiotherapy were adopted, together with simpler techniques, smaller total doses, and larger fraction sizes for the worse prognostic categories. Younger, fit patients are treated more aggressively, more often in association with chemotherapy. Survival did not change over time. The accurate evaluation of neurologic status is therefore of utmost importance before the best treatment option for the individual patient is chosen.

Clinical experience on eight cases of Merkel cell carcinoma.

Merkel cell carcinoma is a rare neuroendocrine neoplasm of the skin. The tumor most frequently affects elderly patients, with a preference for the head and neck. Eight patients affected by Merkel cell carcinoma have been observed at the General Surgery Unit II of the "Istituti Ospitalieri" hospital in Cremona, each in different stages of the disease; 75% of the cases involved the extremities, and in nearly all of the cases the tumor was nodular in appearance, with an average diameter of 2.2 cm. In 2 cases, the tumor was associated with rheumatoid arthritis, suggesting a dependency on the part of the neoplasm on the immune disorder and on steroid treatment. The available data confirm that in stage I of the disease, surgical treatment should be associated with radiotherapy in order to control the development of local relapses or metastases over time. In this stage, we observed a survival of 34 months (range, 24-48). In stages II and III, survival time falls, with very short duration of responses and poor quality of life as a result of the administration of cytotoxic molecules. Bearing in mind that any local relapse tends to appear within 12 months of the removal of the primitive tumor, that lymph node metastases appear in almost half of the patients, and that metastases over time are manifested in over a third of patients, it is essential to adopt a treatment capable of balancing the demand for longer remissions with a better quality of life. In this situation, we observed that treatment with somatostatin analogues achieves interesting responses without side effects, which suggests a close biological relationship between the tumor and somatostatin and that making a careful assessment of the prognostic factors of the disease can guarantee a correct therapeutic choice.

Are international guidelines for the prescription of adjuvant treatment for early breast cancer followed in clinical practice? Results of a population-based study on 1547 patients.

AIMS AND BACKGROUND: The results of several randomized trials and meta-analyses have been reported on adjuvant treatment for early breast cancer and treatment guidelines have been defined accordingly, but detailed data are lacking on the appropriateness of treatment prescription in clinical practice. METHODS: We performed a prospective, observational, multicenter study to monitor the prescription, delivery and effectiveness of radiotherapy following conservative surgery for early breast cancer; 1610 patients treated with postoperative radiation to the breast in 1997 were entered by 12 centers in Lombardy, Italy. Here we report the results of a secondary analysis focused on the prescription of medical adjuvant treatment (1547 eligible patients). RESULTS: Chemotherapy only was prescribed to 526 patients (33%), hormonal therapy only to 539 (33%), and both treatments to 85 patients (5%); 460 women (29%) received no medical adjuvant treatment. We compared the collected data with guidelines defined in 1995 by the St Gallen Consensus Conference. Undertreatment was most frequent in node-negative patients at intermediate/high risk, no treatment (instead of tamoxifen or chemotherapy) being prescribed in 21-45% of cases. Node-negative patients at low risk, on the other hand, were overtreated with tamoxifen in 31% of cases. In node-positive, premenopausal women compliance with guidelines was far better, with a 91-96% rate of chemotherapy prescription. In node-positive, postmenopausal, estrogen receptor-positive patients chemotherapy was unduly prescribed in as many as 56% of cases. Comparison of clinical practice with the next version of the guidelines (1998) showed a somewhat better compliance. CONCLUSIONS: Despite the availability of official and authoritative guidelines, adjuvant treatment prescription for early breast cancer in Lombardy in 1997 was suboptimal, especially in well-defined subgroups of patients.