Sentinel Node Biopsy for Conjunctival Melanoma; Single Centre Experience and Review of Current Literature.

PURPOSE: To evaluate the role of sentinel lymph node (SLN) biopsy in patients with conjuctival melanoma (CjM). STUDY DESIGN: Retrospective observational cohort study and literature review. SUBJECTS: Slovenian patients with CjM are included in the study. METHODS: Prospectively collected data of CjM patients treated from June 2005 to December 2016 were retrospectively analyzed. MAIN OUTCOME MEASURES: The numbers of SLN biopsy procedures, positive and false positive SLN, and local and regional relapses have been described together with overall survival. RESULTS: From June 2005 until December 2016, 24 patients with CjM were treated. The median follow-up time was 65.3 months. The mean Breslow thickness was 1.5 mm (sd = 1.8 mm), and ulceration was present in 29% of cases. Altogether, 14/24 (58%) SLN biopsy procedures were performed. SLN was positive in 2/14 (14%) cases. The estimated 5-year overall survival (OS) of the group was 72.5%, with a median survival of 151 months (95% CI 77-224). From January 2013 to January 2020, five (5/140, 3%) authors reported results comparable to our study. CONCLUSION: Our results confirm that CjM is a rare disease with approximately 14% of positive SLN. At the moment, there are no firm conclusions regarding who would benefit most from SLN biopsy or whether or not CLND should be offered. Data from literature emphasize the need for consistent and uniform staging and future multicentric studies.

Skin Reaction to Cetuximab as a Criterion for Treatment Selection in Head and Neck Cancer.

BACKGROUND/AIM: It can be hypothesized that in patients with locally advanced head and neck cancer and prominent cetuximab (CMb)-induced skin rash, immunoradiotherapy would result in a survival advantage over chemoradiotherapy with cisplatin (CP). PATIENTS AND METHODS: After a loading dose of CMb, one weekly cycle of CMb and CP concurrently with RT, patients who developed a grade ≥2 rash proceeded with immunoradiotherapy, and those with a grade 0-1 rash had chemoradiotherapy. RESULTS: A grade 3-4 allergic reaction to CMb developed in 11/39 (28.2%) patients and further recruitment was stopped. These patients proceeded treatment with CP. In early assessment of skin rash 10/28 patients qualified for chemoradiotherapy and 18/28 patients for immunoradiotherapy. There was no difference in survival between the two groups. CONCLUSION: Rate of serious CMb-induced hypersensitivity reactions was unacceptably high. Even though immunoradiotherapy was administered only to the prognostically most favorable group of patients, it resulted in no advantage over chemoradiotherapy.

Prognostic factors of choroidal melanoma in Slovenia, 1986-2008.

INTRODUCTION: Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. PATIENTS AND METHODS: From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. RESULTS: Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. CONCLUSIONS: It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation.

TPF induction chemotherapy and concomitant irradiation with cisplatin and cetuximab in unresectable squamous cell carcinoma of the head and neck.

BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of docetaxel, cisplatin/5-fluorouracil (TPF) induction chemotherapy and concomitant immunochemoradiotherapy with cetuximab and cisplatin in unresectable head and neck carcinoma. METHODS: Treatment consisted of TPF induction chemotherapy (docetaxel 75 mg/m(2) day 2; cisplatin, 75 mg/m(2) day 2; and 5-fluorouracil 750 mg/m(2) days 1-4; 4 cycles), followed by radiotherapy (RT) and concomitant weekly cetuximab, (250 mg/m(2), after a loading dose of 400 mg/m(2)) and cisplatin (30 mg/m(2)). RESULTS: Twenty-five of 30 patients completed 4 cycles of induction chemotherapy. Six or more concomitant infusions of cisplatin and cetuximab were administered in 13 of 25 and 18 of 25 patients, respectively. The 2-year locoregional control, disease-free survival (DFS), and overall survival (OS) were 47%, 47%, and 50%, respectively. Patients with grade ≥ 2 skin reaction to cetuximab had a superior outcome. CONCLUSION: The tested regimen was effective; however, cetuximab and low-dose cisplatin after induction TPF increased the treatment toxicity. A grade ≥ 2 skin rash correlated with improved efficacy.

Adjuvant radiotherapy for palpable melanoma metastases to the groin: when to irradiate?

PURPOSE: To determine the efficacy of and criteria for postoperative radiotherapy (PORT) in patients with palpable melanoma metastases to the groin. METHODS AND MATERIALS: Patients with palpable metastases to the groin who were treated with therapeutic nodal dissection during 2000 to 2006 were identified in a prospective institutional database. RESULTS: In 101 patients, 103 therapeutic nodal dissections were performed; 37 of these were treated with PORT to a median equivalent dose (eqTD(2)) of 50.6 Gy (range, 50-72 Gy). In the surgery-only and PORT groups, 2-year regional control rates were 86% (95% confidence interval [CI] 76-95%) and 91% (95% CI, 81-100%), respectively (p = 0.395). Of five recurrences in radiation-treated patients, four were of dermal type, and in three of these cases, no bolus over the operative scar was used. PORT improved 2-year regional control (46% [95% CI, 11-82%] vs. 82% [95% CI, 63-100%], p = 0.022) among patients in which the sum of risk factors present (i.e., risk factor score) was ≥2. In multivariate analysis, risk-factor score (<2 vs. ≥2: HR, 2.93; 95% CI, 1.00-8.56; p < 0.0001) and PORT (yes vs. no: HR, 7.81; 95% CI, 2.83-21.74; p = 0.050) was predictive for regional control and on logistic-regression testing, number of involved lymph nodes was predictive for systemic dissemination (p = 0.011). CONCLUSIONS: PORT should follow therapeutic nodal dissection in cases with two or more adverse factors. More conventional fractionation (≤2.5 Gy), cumulative eqTD(2) <60 Gy and use of bolus over the operative scar are recommended.

Melanoma metastases to the neck nodes: role of adjuvant irradiation.

PURPOSE: To review experiences in the treatment of regionally advanced melanoma to the neck and/or parotid with emphasis on the role of adjuvant radiotherapy. PATIENTS AND METHODS: Clinical and histopathologic data, treatment details, and outcomes in patients treated during the period 2000-2006 at the Institute of Oncology, Ljubljana, Slovenia, were reviewed. RESULTS: A total of 40 patients with 42 dissections underwent surgery, and 43 patients with 45 dissections received irradiation postoperatively to a median equivalent dose (eqTD(2): 2 Gy/fraction, 1 fraction/day, 5 fractions/week) of 60 Gy (range, 47.8-78.8). Regional control 2 years after surgery was 56% (95% confidence interval [CI] 40-72%) and after postoperative radiotherapy 78% (CI 63-92%) (p = 0.015). On multivariate analysis, postoperative radiotherapy (yes vs. no: hazard ratio [HR] 6.3, CI 2.0-20.6) and sum of the risk factors present (i.e., risk factor score; HR 1.7 per score point, CI 1.2-2.6) were predictive for regional control. On logistic regression testing, the number of involved nodes was associated with the probability of distant metastases (p = 0.021). The incidence of late toxicity did not correlate with the mode of therapy, eqTD(2), or fractionation pattern. CONCLUSIONS: Adjuvant radiotherapy has the potential to compensate effectively for the negative impact of adverse histopatologic features to disease control in a dissected nodal basin. More conventionally fractionated radiotherapy regimens using fraction doses of 2-2.5 Gy, with cumulative eqTD(2)> or =60 Gy, are recommended. The number of involved lymph nodes is proposed as an additional criterion for limiting the implementation of adjuvant irradiation.

concomitant chemoradiotherapy with mitomycin C and cisplatin in advanced unresectable carcinoma of the head and neck: phase I-II clinical study.

PURPOSE: To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m(2) IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m(2)/d IV, applied during the last 10 fractions of irradiation ("chemoboost"). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m(2)/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m(2)/d (Phase I study), which was tested in the subsequent Phase II study. RESULTS: All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m(2)/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m(2)/d, the corresponding rates were 40%, 20%, and 22%, respectively. CONCLUSION: Concomitant chemoradiotherapy with mitomycin C and cisplatin "chemoboost" at 14 mg/m(2)/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

Successful sphincter-saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy.

Anorectal malignant melanoma is a rare tumor and there is no consensus on whether aggressive or local management is more appropriate. Local sphincter-saving excision has been shown to have a higher recurrence rate than abdominoperineal resection, although there is no long-term survival difference between the two approaches. Therefore, new adjuvant treatment strategies to permit local sphincter-saving excisions are warranted. In our case, a large anorectal malignant melanoma was successfully treated preoperatively by electrochemotherapy with cisplatin that, by reducing the tumor size, enabled sphincter-saving local excision. Brachytherapy was postoperatively delivered to the excision site. Fourteen months after the beginning of treatment, the patient is without signs of local recurrence and is continent.

Echographic follow-up of malignant melanoma of the choroid after brachytherapy with 106Ru.

BACKGROUND: The objective of this study was to analyse the dynamics and importance of different choroidal melanoma echographic parameters (height, base diameter, volume and internal reflectivity) after (106)Ru brachytherapy (BT Ru) and to assess at what time after treatment it is most appropriate to evaluate the outcome. PATIENTS AND METHODS: A retrospective study was performed in 65 patients. The mean height of tumours was 4.8 mm. The mean dose to the tumour apex was 100 Gy. The patients were followed-up for a period of 22 to 169 months. RESULTS: With regard to the treatment outcome, the patients were categorised into three groups: successfully treated patients, in whom the tumour regressed with no metastatic spread, unsuccessfully treated patients, in whom enucleation was required because of the recurrence or further growth, and deceased patients. The largest decrease of tumour size was observed within 12 months after brachytherapy. The groups of deceased and successfully treated patients did not significantly differ as to the extent and rate of tumour decrease. In the local failure group, the tumour decrease in the first year after brachytherapy was less than in the other two groups. CONCLUSIONS: To follow-up the regression of the malignant melanoma of the choroid after brachytherapy with (106)Ru, the most reliable measurements were those of the tumour height. In the tumours that regressed, it is appropriate to evaluate the efficiency of treatment one year after brachytherapy. Recurrent growth may be expected in the tumours that regressed poorly.