ABSTRACT
BACKGROUND: Intra-lesional interleukin 2 (IL-2) therapy trials for the treatment of in-transit melanoma using different treatment protocols have been published reporting varied results. This study assesses the results of IL-2 therapy in our institution and to evaluate the reproducibility of our response rates when using the same treatment protocol as another Canadian centre. METHODS: A retrospective review was undertaken of patients with in-transit melanoma who were treated with intralesional IL-2 in a single institution from 2010 to 2016. Responses were evaluated using RECIST criteria. Demographic data, tumour characteristics, follow-up data, in-transit-free interval, and survival data were collected and analysed. RESULTS: Forty-nine patients were identified. Overall tumour response rate was 72%, including complete response in 23 patients (47%) and partial response in 12 patients (24%). Stable disease was observed in 4% of patients and progressive disease in 25%. The main side effects were minor discomfort with injections and auto-limited flu-like symptoms. The presence of tumour-infiltrating lymphocytes may be a predictor of better response. CONCLUSION: This study confirms prior experience with intra-lesional IL-2, demonstrating it to be an effective, safe, and well-tolerated therapy for in-transit melanoma. Tumour-infiltrating lymphocytes as a predictor of better response warrant further study.
HISTORIQUE: Les publications sur l'utilisation d'interleukine-2 (IL-2) intralésionnelle pour traiter les mélanomes en transit faisant appel à divers protocoles thérapeutiques ont rendu compte de résultats variables. Dans la présente étude, les chercheurs évaluent les résultats du traitement à l'IL-2 au sein de leur établissement et la reproductibilité de leur taux de réponse lorsqu'ils utilisent le même protocole thérapeutique qu'un autre centre canadien. MÉTHODOLOGIE: Les chercheurs ont effectué une analyse rétrospective des patients atteints d'un mélanome en transit qui ont reçu de l'IL-2 intralésionnelle dans un même établissement entre 2010 et 2016. Ils ont évalué les réponses selon les critères d'évaluation RECIST et ont colligé et analysé les données démographiques, les caractéristiques des tumeurs, les données de suivi, l'intervalle libre en transit et les données de survie. RÉSULTATS: Les chercheurs ont dénombré 49 patients. Le taux de réponse global des tumeurs s'élevait à 72 %, y compris une réponse complète chez 23 patients (47 %) et une réponse partielle chez 12 patients (24 %). Ils ont observé une maladie stable chez 4 % des patients et une maladie évolutive chez 25 % d'entre eux. Les principaux effets secondaires étaient des malaises mineurs à l'injection et des symptômes pseudogrippaux autolimités. L'infiltration lymphocytaire des tumeurs pourrait être un élément prédicteur d'une meilleure réponse. CONCLUSION: La présente étude confirme l'expérience antérieure de l'IL-2 intralésionnelle et démontre qu'il s'agit d'un traitement efficace, sécuritaire et bien toléré contre le mélanome en transit. D'autres études devront être réalisées pour établir si l'infiltration lymphocytaire des tumeurs est un bon élément prédicteur.
ABSTRACT
BACKGROUND: Intralesional injection of interleukin-2 (IL-2) for in-transit melanoma (ITM) is associated with a high rate of complete response. However, there is a paucity of data on treatment durability and long-term outcomes. OBJECTIVES: To provide long-term data on patients with a complete response to IL-2 therapy for ITM. METHODS: Consecutive patients with ITM, treated with intralesional IL-2 therapy, at the Tom Baker Cancer Center were identified from April 2009 to August 2019. All patients received at least 4 cycles (every 2 weeks) of IL-2 (5 MIU/mL). Complete response was defined as sustained (ie, 3 months) clinical complete remission of all known in-transit disease. RESULTS: Sixty-five patients were treated with curative intent for in-transit disease with intralesional IL-2. Complete clinical response was identified in 44.6% (29/65). In this subset of patients, the median number of lesions per patient was 9 (range 1-40). The median total dose of IL-2 was 0.8 mL (IQR 0.4-1.5) per lesion. One patient received isolated limb infusion and 13.8% (4/29) received systemic immunotherapy as part of their initial management. At a median follow-up of 27 months (IQR 16-59), 34.5% (10/29) developed recurrent disease. Of these patients, 50.0% (5/10) presented with synchronous in-transit and distant metastases. The median time to recurrence was 10.5 months (IQR 5.8-16.3). CONCLUSION: With long-term follow-up, 65.5% of complete responders have a durable response to intralesional IL-2 therapy. In this cohort of patients, local in-transit recurrence is most likely to occur within 12 months and is often associated with concomitant distant disease.
Subject(s)
Interleukin-2/administration & dosage , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Injections, Intralesional , Male , Melanoma/pathology , Middle Aged , Neoplasm Recurrence, Local , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Preoperative irradiation reduces local recurrence of soft tissue sarcomas (STSs), but major wound complication rates approach 25-35 %. Using a novel neoadjuvant chemoradiation protocol, we prospectively documented functional outcomes and quality of life (QOL) and hypothesized a lower major wound complication rate. METHODS: Patients with STS deep to muscular fascia were treated with 3 days of doxorubicin (30 mg/day) and 10 days of irradiation (300 cGy/day) followed by limb-sparing surgery. Wound complications were assessed, and functional assessment and QOL were followed prospectively using the Toronto Extremity Salvage Score (TESS), Musculoskeletal Tumor Society (MSTS), and Short Form (SF)-36 questionnaires preoperatively and 6 and 12 months postoperatively. RESULTS: Altogether, 52 consecutive patients were accrued during 2006-2011. Overall, 80.8 % of STSs were >5 cm, and 67.3 % involved the lower extremity. Seven (13.5 %) major wound complications occurred, all requiring reoperation. Preoperative scores for TESS, MSTS, and SF-36 physical (PCS) and mental (MCS) health components were 83.3, 86.7, 40.6, and 49.4, respectively. There were no differences seen 6 months postoperatively. By 12 months, however, patients showed improved functional scores (TESS 93.0, p = 0.02; MSTS 93.3, p < 0.01) and QOL scores (PCS 45.1, p = 0.02; MCS = 52.9, p = 0.05). No differences in scores were seen between patients with or without wound complications. CONCLUSIONS: Patients treated with our neoadjuvant chemoradiation protocol had stable QOL and functional scores 6 months postoperatively and showed improvement by 12 months. Importantly, the major wound complication rate was low.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Neoadjuvant Therapy , Quality of Life , Sarcoma/complications , Wounds and Injuries/etiology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Limb Salvage , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Preoperative Care , Prognosis , Prospective Studies , Young AdultABSTRACT
Intra-lesional interleukin-2 (IL-2) is effective in treating in transit melanoma metastases. Results from multiple studies were examined to evaluate the efficacy of IL-2 for in transit disease. In the published literature, complete response ranged from 0% to 69% per patient, and 41% to 96% per lesion, with excellent tolerability. Combining the results of six studies show complete response in 50% of patients and 78% of lesions. Intra-lesional IL-2 should be considered early in the course of treatment for in transit disease, ahead of other, more toxic therapies.
