Outcomes of older adults aged 90 and over with cutaneous malignancies after electrochemotherapy with bleomycin: A matched cohort analysis from the InspECT registry.

BACKGROUND: With extending life expectancy, more people are diagnosed with cutaneous malignancies at advanced ages and are offered nonsurgical treatment. We assessed outcomes of the oldest-old adults after electrochemotherapy (ECT). METHODS: The International Network for Sharing Practices of ECT (InspECT) registry was queried for adults aged ≥90 years (ys) with skin cancers/cutaneous metastases of any histotype who underwent bleomycin-ECT (2006-2019). These were subanalysed with patients aged <90 ys after matching 1:2 for tumor location, number, size, histotype, and previous treatments. We assessed ECT modalities, toxicity (CTCAE), response (RECIST), and patient perception (EQ-5D). RESULTS: Sixty-one patients represented the study cohort (median 92 ys, range 92-104), 122 the control group (median 77 ys, range 23-89). Among the oldest-old, 44 patients (72%) had primary/recurrent skin cancers, 17 (28%) cutaneous metastases. Median tumour size was 15 mm (range, 5-450). The oldest-old adults underwent ECT mainly under local/regional anaesthesia (59% vs 39% p = .012). We observed no differences regarding dose and route of chemotherapy (intravenous vs intratumoral, p = .308), electrode geometry (linear vs hexagonal, p = .172) and procedural duration (18 vs 21 min, p = .378). Complete response (57.4 [95%-CI 44.1%-70.0%] vs 64.7% [95%-CI 55.6%-73.2%], p = .222) and 1-year local control (76.7% vs 81.7, p = .092) rates were comparable. Pain and skin hyperpigmentation were mild in both groups. Skin ulceration persisted longer in the oldest-old patients (4.4 vs 2.4 months, p = .008). CONCLUSIONS: The oldest-old adults with cutaneous malignancies undergo ECT most commonly under local/regional anaesthesia with safety profiles and clinical effectiveness similar to their younger counterparts, except in case of ulcerated tumors.

Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008-2016.

AIM: Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). METHODS: Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients' characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2-, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. RESULTS: The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7-40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p < 0.0001) with a median OS of 43.3 (95% CI, 42.5-44.5) in HR+/HER2-; 50.1 (95% CI, 47.6-53.1) in HER2+; and 14.8 months (95% CI, 14.1-15.5) in triple-negative subgroups, respectively. Beyond performance status, the following variables had a constant significant negative prognostic impact on OS in the whole cohort and among subtypes: older age at diagnosis of metastases (except for the triple-negative subtype), metastasis-free interval between 6 and 24 months, presence of visceral metastases and number of metastatic sites ≥ 3. CONCLUSIONS: The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. DATABASE REGISTRATION: clinicaltrials.gov Identifier NCT032753.

Multiple sites of soft-tissue metastases secondary to lung cancer: A case report.

RATIONALE: The prognosis of lung cancer is dismal, which has resulted in lung carcinoma being one of the leading causes of cancer-related deaths worldwide. Non-small cell lung cancer accounts for approximately 80% of all types of lung carcinoma. The skeletal system and central nervous system are the most common distal metastatic sites in patients with lung cancer, while cutaneous and soft tissues metastasis is rare. PATIENT CONCERNS: We report a case of concomitant metastasis in the nasal tip and suspected buttocks metastasis secondary to lung cancer, who complained of repeated cough and white sputum for 6 months. DIAGNOSE: Primary lung cancer was diagnosed by bronchoscopy and biopsy, lesion on nasal tip was confirmed by biopsy. Furthermore, PET-CT scan identified the untouchable buttocks lesion that could have been easily missed. INTERVENTIONS: This patient refused systemic treatments, but he chose traditional Chinese medicine at home. OUTCOMES: He died 6 months after the diagnosis. LESSONS: The possibility of metastasis of primary cancers should be considered when encountering soft-tissue neoplasm lesions, and a biopsy of the suspicious cutaneous lesions could likely aid in the histological identification of the primary cancer. PET-CT scan could be an effective supplementary tool for the diagnosis and evaluation of cancers.

Management of Chronic Hypotony Following Bilateral Uveitis in a Patient Treated with Pembrolizumab for Cutaneous Metastatic Melanoma.

Purpose: To describe the presentation and management of severe ocular adverse events following treatment with pembrolizumab for cutaneous metastatic melanoma. Methods: Interventional case report. Results: A 73-year-old Caucasian man receiving pembrolizumab treatment for metastatic melanoma presented with panuveitis and subsequent profound hypotony, choroidal effusions, and optic disk swelling bilaterally. Oral prednisolone controlled intraocular inflammation. However, bilateral hypotony persisted which was managed over a 12-month period with ocular viscoelastic device injections into the anterior chamber of both eyes. There was also phacoemulsification with pars plana vitrectomy (PPV) and silicone oil (SO) tamponade performed on the left eye only. Intraocular pressure (IOP) stabilized (>6 mmHg) with best-corrected visual acuity of 6/60. Conclusion: We report a severe adverse event from pembrolizumab therapy resulting in uveitis and persistent hypotony. Repeat injections of high viscosity OVD achieved an increase in IOP up to 12 months. This technique may be a useful adjuvant or alternative to PPV and SO.

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

BACKGROUND: Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure. METHODS: All patients who underwent resection of primary MCC at a single institution from 2000 to 2015 were reviewed. Patient demographics, clinicopathologic characteristics, treatments, and outcomes were reviewed. RESULTS: A total of 240 patients underwent resection of primary MCC with resection margin width identified in the operative report. The median age was 76 years, and 65.8% of the patients were men. Of the 240 patients, 85 (35.4%) had head and neck primaries, 140 (58.3%) had extremity primaries, and 15 (6.3%) had trunk primaries. In terms of margins, 69 patients (28.8%) had a margin of 1 cm, 36 patients (15%) had a margin of 1.1-1.9 cm, and 135 patients (56.2%) had a margin of 2 cm or more. The median follow-up period was 21 months. The LR rate was 2.9% for a margin of 1 cm, 2.8% for a margin of 1.1-1.9 cm, and 5.2% for a margin of 2 cm or more (p = 0.80). The 5-year OS was 63.6% for a margin of 1 cm, 59.7% for a margin of 1.1-1.9, and 70.7% for a margin of 2 cm or more (p = 0.66). The 5-year DSS was 80.3% for a margin of 1 cm, 66.2% for a margin of 1.1-1.9 cm, and 91.8% for a margin of 2 cm or more (p = 0.28). For wound closure, 43.5, 50, and 65.9% of the patients respectively required a flap or graft with a margin of 1, 1.1-1.9, and 2 cm or more (p = 0.006). CONCLUSIONS: A 1-cm resection margins did not increase the risk of LR. Margin width did not make a significant difference in DSS or OS. Larger resection margins increase the need for a graft or flap closure.

Metástasis cutáneas de adenocarcinoma de próstata / Cutaneous Metastases From Adenocarcinoma of the Prostate

No disponible

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma.

BACKGROUND: In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction. METHODS: An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy. Patients had in-transit melanoma metastases suitable for IL therapy and radiotherapy. RESULTS: Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis (CR 33.3%, PR 53.3%, SD 6.7%). The median follow up duration was 19.25 months. Size of metastases (<10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events. CONCLUSIONS: The combination of PV-10 and radiotherapy resulted in lesion-specific, normal tissue-sparing, ablation of disease with minimal local or systemic adverse effects.

Costs associated with Eribulin treatment for patients with metastatic breast cancer in a comprehensive cancer center in France.

BACKGROUND: There is no standard recommendation for metastatic breast cancer treatment (MBC) after two chemotherapy regimens. Eribulin (Halaven®) has shown a significant improvement in overall survival (OS) in this setting. Its use may however be hampered by its cost, which is up to three times the cost of other standard drugs. We report the clinical outcomes and health care costs of a large series of consecutive MBC patients treated with Eribulin. METHODS: A monocentric retrospective study was conducted at Institut Curie over 1 year (August 2012 to August 2013). Data from patient's medical records were extracted to estimate treatment and outcome patterns, and direct medical costs until the end of treatment were measured. Factors affecting cost variability were identified by multiple linear regressions and factors linked to OS by a multivariate Cox model. RESULTS: We included 87 MBC patients. The median OS was 10.7 months (95%CI = 8.0-13.3). By multivariate Cox analysis, independent factors of poor prognosis were an Eastern Cooperative Oncology Group (ECOG) performance status of 3, a number of metastatic sites ≥ 4 and the need for hospitalization. Per-patient costs during whole treatment were €18,694 [CI 95%: 16,028-21,360], and €2581 [CI 95%: 2226-3038] per month. Eribulin administration contributed to 79% of per-patient costs. CONCLUSIONS: Innovative and expensive drugs often appear to be the main cost drivers in cancer treatment, particularly for MBC. There is an urgent need to assess clinical practice benefits.

[Two Year Recurrence Free Survival after Resection of Cutaneous Metastasis from Pancreatic Cancer - A Case Report].

The patient was a 73-year-old woman who underwent distalpancreatectomy for pancreas tailcancer (T3, N0, M0, stage III ). Hepatic arterialinfusion(HAI)using high-dose 5-fluorouracil(5-FU)(6,000mg/week)was performed 35 days after curative resection to prevent liver metastases. Although chemotherapy with gemcitabine(GEM)was administered for 2 weeks, the patient was aware of a nodule(1 cm in diameter)on the right lower quadrant of the abdomen. Resection of the cutaneous mass was performed and histological findings revealed metastatic adenocarcinoma from the pancreas cancer. Six courses of chemotherapy with GEM were administered as adjuvant therapy. Two years after the treatment with GEM, neurological symptoms appeared, and computed tomography(CT)and magnetic resonance imaging(MRI)revealed a solitary metastatic thalamus tumor(2 cm in diameter). After stereotactic radiotherapy, the patient was transferred to a different hospitalfor physicaltherapy. Herein, we report on a case of 2 year recurrence free survivalafter the resection of a cutaneous metastasis from pancreatic cancer.

Predicting patients at risk for pain associated with electrochemotherapy.

BACKGROUND: Electrochemotherapy describes the use of electric pulses to enhance chemotherapy uptake, and has proven highly efficient in treating cutaneous metastases. Patients referred for electrochemotherapy present with diverse clinical pictures, from multiple small lesions to large, ulcerated lesions. Post-electrochemotherapy pain has been observed in some patients. The objectives of this study were to evaluate pain scores before and after electrochemotherapy, and to investigate if patients at risk of post-procedure pain could be identified. METHODS: Seven cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively reported to a common database. Electrochemotherapy consisted of intratumoural or intravenous injection of bleomycin, followed by delivery of electric pulses in local or general anesthesia. RESULTS: Of 121 patients 39% had metastatic melanoma, 18% squamous cell carcinoma, 16% breast cancer, 13% basal-cell carcinoma, and 14% other malignancies. Median size of the largest nodules was 2.3 cm (range 0.3-40 cm). A majority of patients presented with low pain scores, and this continued through follow-up (74%). A subset of patients had moderate (13%) or severe pain (13%) after treatment. Post-procedure pain was statistically significantly associated with: 1) moderate or severe pain before treatment (p<0.0001); 2) size of the largest treated lesion (p<0.01); 3) previous irradiation (p<0.02); and 4) high treatment current value (p<0.0001). CONCLUSION: The majority of patients had no or mild pain after electrochemotherapy. Patients at risk for post-procedure pain could be identified at the pre-treatment visit, and/or at the time of treatment, enabling a pain management strategy for this group.

Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma.

PURPOSE: This international, multicenter, single-arm trial assessed efficacy and safety of intralesional rose bengal (PV-10) in 80 patients with refractory cutaneous or subcutaneous metastatic melanoma. METHODS: Sixty-two stage III and 18 stage IV melanoma patients with disease refractory to a median of six prior interventions received intralesional PV-10 into up to 20 cutaneous and subcutaneous lesions up to four times over a 16-week period and were followed for 52 weeks. Objectives were to determine best overall response rate in injected target lesions and uninjected bystander lesions, assess durability of response, and characterize adverse events. RESULTS: For target lesions, the best overall response rate was 51 %, and the complete response rate was 26 %. Median time to response was 1.9 months, and median duration of response was 4.0 months, with 8 % of patients having no evidence of disease after 52 weeks. Response was dependent on untreated disease burden, with complete response achieved in 50 % of patients receiving PV-10 to all of their disease. Response of target lesions correlated with bystander lesion regression and the occurrence of locoregional blistering. Adverse events were predominantly mild to moderate and locoregional to the treatment site, with no treatment-associated grade 4 or 5 adverse events. CONCLUSIONS: Intralesional PV-10 yielded durable local control with high rates of complete response. Toxicity was confined predominantly to the injection site. Cutaneous bystander tumor regression is consistent with an immunologic response secondary to ablation. This intralesional approach for local disease control could be complementary to current and investigational treatments for melanoma.

Clinical Course of a Presumed Metastatic Uveal Melanoma to the Contralateral Choroid.

We present the ultrasound and optic coherence tomography follow-up of a presumed choroidal metastasis from a contralateral melanoma. A 53-year-old male was diagnosed with uveal melanoma with extraescleral extension in his left eye. A year later, the fundus examination revealed a flat, gray-green, pigmented choroidal lesion in the right eye. The ultrasonography showed a mass, almost flat, and all these findings were compatible with a choroidal melanocytic lesion with risk factors for growth. One month later, melanocytic skin lesions appeared on the scalp, as well as small tumors. Three months later, an ultrasonography on B scan showed a growth of the tumor size. The patient developed a progressive deterioration and died. Three possibilities can explain the occurrence of a choroidal pigmented tumor in the contralateral eye: first, bilateral primary choroidal melanomas; second, both choroidal tumors are metastatic in origin from an unknown primary melanoma; and third, the contralateral tumor is a metastatic tumor from the primary choroidal melanoma.

Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma.

INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL AND METHODS: A total of 84 perfusions were performed (53 women, 31 men, median age 63 years) from 1993 to 2010. 95% of the perfusions were administered to the lower limbs and 5% to the upper limbs. The inclusion criteria were recurrent and/or clinically apparent cutaneous/subcutaneous extremity in-transit melanoma metastases. RESULTS: The response rate after ILP was 85%; 42% had complete response (CR), 43% partial response (PR), 12% no change (NC) and 3% progression. Two- and five-year survival rates were 57% and 31%, respectively, and they were higher for patients with than without lymph node metastases. Time from ILP to recurrence was a median of seven months (range 1-37 months) for patients with CR or PR. Survival was longer for patients with CR or PR than for patients showing NC or progression. Several patients had mild or moderate local toxicity reactions, two patients developed severe local toxicity. CONCLUSION: ILP induces tumour regression in the vast majority of patients. One patient, i.e. 1% of the group, died from surgical complications. Otherwise, ILP treatment had an acceptable morbidity in this group of very sick patients. We are convinced that the treatment should be offered to improve local disease control in patients with multiple and/or recurrent melanoma confined to an extremity if surgical excision is not possible. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Unusual long-lasting cutaneous complete response to lapatinib and capecitabine in a heavily pretreated HER2-positive plurimetastatic breast cancer patient.

Lapatinib, in combination with capecitabine, has shown clinical activity in both first-line and refractory disease in patients with HER2-positive advanced breast cancer. Herein we describe the case of a plurimetastatic, heavily pretreated, HER2-positive breast cancer patient who experienced multiple cutaneous metastases successfully treated with lapatinib and capecitabine. An early complete response was obtained on all skin lesions, and no evidence of disease progression at other metastatic sites was observed for 22 months. The treatment was well tolerated, without dose-reductions or delays. In advanced breast cancer patients with skin metastases overexpressing HER2, previously treated with anthracyclines, taxanes and trastuzumab, lapatinib and capecitabine may represent a very active, safe and well-tolerated treatment option.

Supportive and palliative care for metastatic breast cancer: resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement.

Many women diagnosed with breast cancer in low- and middle-income countries (LMICs) present with advanced-stage disease. While cure is not a realistic outcome, site-specific interventions, supportive care, and palliative care can achieve meaningful outcomes and improve quality of life. As part of the 5th Breast Health Global Initiative (BHGI) Global Summit, an expert international panel identified thirteen key resource recommendations for supportive and palliative care for metastatic breast cancer. The recommendations are presented in three resource-stratified tables: health system resource allocations, resource allocations for organ-based metastatic breast cancer, and resource allocations for palliative care. These tables illustrate how health systems can provide supportive and palliative care services for patients at a basic level of available resources, and incrementally add services as more resources become available. The health systems table includes health professional education, patient and family education, palliative care models, and diagnostic testing. The metastatic disease management table provides recommendations for supportive care for bone, brain, liver, lung, and skin metastases as well as bowel obstruction. The third table includes the palliative care recommendations: pain management, and psychosocial and spiritual aspects of care. The panel considered pain management a priority at a basic level of resource allocation and emphasized the need for morphine to be easily available in LMICs. Regular pain assessments and the proper use of pharmacologic and non-pharmacologic interventions are recommended. Basic-level resources for psychosocial and spiritual aspects of care include health professional and patient and family education, as well as patient support, including community-based peer support.

Electrochemotherapy under tumescent local anesthesia for the treatment of cutaneous metastases.

BACKGROUND: The surgical management of cutaneous metastasis (CM) is challenging, particularly in elderly patients, in whom general anesthesia can be difficult because of comorbidity. OBJECTIVES: To test the effectiveness of tumescent local anesthesia (TLA) to achieve adequate anesthesia during the treatment of extensive CM with electrochemotherapy (ECT), previously only performed under general anesthesia. METHODS: We conducted five ECT treatments of CM with intralesional bleomycin under TLA. We examined pain scores before, during, and after treatment; analgesic use; and side effects. The intention of the treatment was palliative in all cases. RESULTS: We treated four patients (ages 75-88) with CM with a mean area of 126 cm(2) (range 12-198 cm(2) ) with 356 mL of TLA per treatment (range 180-450 mL). The ECT treatment under TLA demonstrated that anesthesia was adequate, with moderate pain during and slight pain after the procedure as measured on a visual analog scale (VAS). CONCLUSIONS: In this proof-of-principle study, we demonstrated that ECT can be performed under TLA; TLA might be a useful new anesthesia option for patients treated with ECT.

Collagen sealant patch to reduce lymphatic drainage after lymph node dissection.

BACKGROUND: Seroma formation is a frequent complication following radical lymph node dissection (RLND) in patients with metastatic melanoma. Several strategies have been used to prevent fluid accumulation and thereby reduce the duration of postoperative drainage, including fibrin sealants. METHODS: This was a prospective, single-center study in which consecutive patients undergoing surgical treatment of stage III metastatic melanoma by axillary or ilio-inguinal RLND were randomized to receive standard treatment plus fibrinogen/thrombin-coated collagen sealant patch (CSP) or standard treatment alone. The primary endpoint of the study was postoperative duration of drainage. RESULTS: A total of 70 patients underwent axillary (n = 47) or ilio-inguinal (n = 23) RLND and received CSP plus standard treatment (n = 37) or standard treatment alone (n = 33). Mean duration of drainage was significantly reduced in the CSP group compared with standard treatment (ITT analysis: 20.1 ± 5.1 versus 23.3 ± 5.1 days; p = 0.010). The percentage of patients drainage-free on day 21 was significantly higher in the CSP group compared with the standard treatment group (86% versus 67%; p = 0.049). CONCLUSIONS: Use of the tissue sealant resulted in a significant reduction in duration of drainage. Further studies are warranted to confirm these results in different and selected types of lymphadenectomy.