Noncontrast-enhanced 3-Tesla MRI using surface coil as a complementary test for assessment of distribution and depth of locoregional cutaneous metastases of malignant melanoma.

Locoregional and distant metastases account for most cases of morbidity and mortality associated with melanoma. In addition, local recurrences of melanoma might be the onset of disseminated disease. Therefore, precise diagnosis and therapy are warranted to minimize morbidity and increase survival in a subset of patients. However, the correct distribution of the metastatic lesions on the skin is often difficult to estimate. We present the application of noncontrast-enhanced 3-Tesla MRI using surface coil to detect locoregional cutaneous metastases of malignant melanoma on the basis of the topographic assessment of skin lesions. Furthermore, in a systematic review, we summarize the current knowledge about application of MRI in assessment of location, distribution, and depth of cutaneous primary malignant melanoma. MRI might be applied to evaluate the location, distribution, size, and depth of the locoregional cutaneous metastasis of malignant melanoma to identify the optimal cost-effective treatment strategies and monitor their effects.

Socioeconomic Status and Melanoma in Canada: A Systematic Review.

As melanoma is one of the leading cancers in average years of life lost per death from disease, screening and early diagnosis are imperative to decrease morbidity and mortality. Socioeconomic status (SES) has been shown to be associated with melanoma incidence. However, it is unclear if this association holds true in universal healthcare systems where screening, diagnostic, and treatment services are available to all patients. The objective of this systematic review was to evaluate the evidence on the association of SES and melanoma incidence in Canada. A comprehensive search of PubMed and EMBASE yielded 7 studies reporting on melanoma incidence or outcomes with respect to SES in Canada. High SES was associated with increased melanoma incidence across all studies, which encompassed all Canadian provinces, and time periods spanning from 1979 to 2012. Studies also reported an increasing incidence of melanoma over time. There were substantial discrepancies in melanoma incidence across Canadian provinces, after controlling for SES and demographic characteristics. Populations of lower SES and living within certain healthcare regions had increased risks of advanced melanoma at diagnosis. This review highlights the potential for inequities in access to care even within a universal healthcare system. Future research is needed to characterize specific risk factors within different patient groups and within the universal health system context in order to implement targeted strategies to lower melanoma incidence, morbidity, and mortality.

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.

Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

BACKGROUND: Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. METHODS: ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. RESULTS: Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. CONCLUSIONS: EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

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.

Delay of Surgery for Melanoma Among Medicare Beneficiaries.

IMPORTANCE: Timely delivery of surgery for cancer affects health care quality and outcomes. However, population-based studies characterizing the delay of surgery for melanoma in the United States have not been performed. OBJECTIVE: To assess the delay of surgery for melanoma by tumor-, patient-, and physician-level characteristics. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of Medicare beneficiaries diagnosed as having melanoma from January 1, 2000, through December 31, 2009, using the Surveillance, Epidemiology, and End Results-Medicare database. We included all patients undergoing surgical excision of melanoma diagnosed by means of results of skin biopsy. EXPOSURES: Anatomic location and stage of the tumor, patient sociodemographic characteristics, prior melanoma, Elixhauser comorbidities, and the specialties of the physicians who performed the biopsy and surgery. MAIN OUTCOMES AND MEASURES: Surgical delay, measured as the time from the biopsy to surgical excision. We estimated risk-adjusted odds ratios (ORs) and marginal probabilities of delay with 95% CIs for each covariate using mixed-effects logistic regression. RESULTS: Our cohort consisted of 32 501 cases of melanoma. Most of the patients were white (95.4%), male (63.1%), married (47.9%), and 75 years or older (60.8%) and did not have a prior melanoma (93.7%). Melanomas were most frequently located on the head and neck (40.5%) and staged as in situ disease (48.2%). More than three-quarters of cases (25 269 [77.7%]) underwent excision within 1.5 months of biopsy. Among those treated after 1.5 months (7232 [22.3%]), 2620 (8.1% of all cases) experienced a delay of longer than 3 months. The incidence of a risk-adjusted surgical delay longer than 1.5 months was significantly increased among patients 85 years or older compared with those younger than 65 years (odds ratio [OR], 1.28 [95% CI, 1.05-1.55]; P = .02), those with a prior melanoma (OR, 1.20 [95% CI, 1.08-1.34]; P = .001), and those with an increased comorbidity burden (OR, 1.18 [95% CI, 1.09-1.27]; P < .001). Melanomas that underwent biopsy and excision by dermatologists had the lowest likelihood of delay (probability, 16% [95% CI, 14%-18%]). The highest likelihood of delay (probability, 31% [95% CI, 24%-37%]) occurred when the biopsy was performed by a nondermatologist and excised by a primary care physician. Similar findings were observed for a delay longer than 3 months. CONCLUSIONS AND RELEVANCE: Approximately 1 in 5 Medicare beneficiaries experience a delay of surgery for melanoma that is longer than 1.5 months. Those patients undergoing biopsy and surgery by dermatologists have the lowest risk for delay, highlighting potential opportunities for improved access to and coordination of dermatologic care.

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.

High-frequency 30-MHz sonography in preoperative assessment of tumor thickness of primary melanoma: usefulness in determination of surgical margin and indication for sentinel lymph node biopsy.

BACKGROUND: High-frequency sonographic imaging has been used for the preoperative evaluation of primary malignant melanoma. In the present study, to identify the usefulness of 30-MHz sonography for determination of the surgical margin and indication for sentinel lymph node biopsy, the correlation between sonometric and histometric tumor thickness was investigated. METHODS: A total of 74 primary melanomas, in patients seen at the dermatology clinic, Shinshu University Hospital, from 1998 to 2006, were evaluated using high-frequency sonographic equipment with two probes (15 MHz and 30 MHz), and tumor thickness was measured using electronic calipers before surgical treatment. All the primary lesions were surgically excised and Breslow's tumor thickness was measured histologically. RESULTS: In 68 melanomas, excluding 2 lesions of melanoma in situ and 4 lesions with poor sonographic images, sonographic and histologic thickness showed good correlation (r = 0.887). Particularly, in 26 melanomas affecting the soles of the feet, sonographic and histologic thickness showed excellent correlation (r = 0.945). Regarding the T categorization, in which T1-T4 are divided at 1, 2, and 4 mm in thickness, the categories determined with sonometry corresponded very well to those determined with histometry. The correspondence was particularly excellent in thinner primary lesions with thickness around 1 mm. We excised almost all these primary melanomas with surgical margins based on the sonometric thickness. In 22 patients with sonometric thickness more than 1 mm, sentinel lymph node biopsy and/or radical lymphadenectomy was performed. CONCLUSION: High-frequency sonography (30-MHz) is very useful in the preoperative prediction of tumor thickness, particularly in thinner primary lesions, which allows us to determine surgical margins and indication for sentinel lymph node biopsy.

Incidence of port-site metastasis after laparoscopic management of borderline ovarian tumors: a series of 22 patients.

PURPOSE: The aim of this work was to evaluate the incidence of port-site metastasis in patients undergoing laparoscopy for borderline ovarian carcinoma (BOT). METHODS: Twenty-two patients who underwent laparoscopy from 2004 to 2008 for BOT were evaluated retrospectively. RESULTS: In 15 patients an ultraconservative procedure with enucleation of the annexal neoplasia was carried out, while in five (23%) unilateral salpingo-oophorectomy was performed and in two cases (9%) bilateral salpingo-oophorectomy was done. CONCLUSION: The literature data report few cases of port-site metastasis in BOT patients. Residual cutaneous metastases have been reported to occur within 12 months from the first surgery, generally in association with serous histology. In our analysis, we found 17 out of 22 cases of serous BOT, three mucinous and two endometriod. In no case was cutaneous metastasis revealed after an average of 30 months of follow-up.

The malignant wound assessment tool: a validation study using a Delphi approach.

Malignant wounds, caused by the direct invasion of cancer into the skin, occur in cancer patients with primary skin tumours and as cutaneous metastasis in approximately 10% of patients with metastatic internal malignancies. Malignant wounds have a profound impact on patients, family members and health care providers. The assessment of the patient with malignant wounds can be complex and there is no widely accepted, consistent approach. Valid, descriptive survey research methods were used to develop the Malignant Wound Assessment Tool (MWAT). The authors developed two versions of the MWAT: a brief clinical version (MWAT-C) and a more detailed research version (MWAT-R). Domains include clinical wound features, physical effects and emotional and social impacts of the wound. The two tools underwent content and construct validity testing using a Delphi process. An international panel of professionals with clinical or research expertise related to malignant wounds was formed. Panelists participated in two rounds of review for each tool. Development and face validity testing of the MWAT-C and MWAT-R tools through the Delphi process have resulted in tools ready for clinical application and will support clinical and research activities to improve care for patients with this devastating condition.

Use of the monoclonal antibody anti-HER2 trastuzumab in the treatment of metastatic breast cancer: a cost-effectiveness analysis.

BACKGROUND: This open controlled prospective study aimed at evaluating the medical and economical impact of first line chemotherapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: Two groups of HER +++ MBC patients were compared: 26 were treated by a combination of trastuzumab and paclitaxel in 4 "prescriber" centers (group A) and 19 patients were treated by any chemotherapy without addition of trastuzumab, in 6 control centers (group B). The cost of chemotherapy and related hospitalizations was taken into account during the first 8 cycles. RESULTS: Forty-five patients, mean age 51 years have been included. The objective response rate was significantly higher in group A (42% vs. 6%, P = 0.036). The median overall survival was 17 months longer in the group A (29 vs. 12 months). The median progression free survival rate was 12.2 months longer in the group A (19 vs. 7 months). The 1-year survival rate was 85% in the group A and 47% in the group B. The mean overall care cost was 33.271 euro per patient in group A versus 11.191 euro per patient in group B. The additional cost per saved year of life expressed as the incremental cost-effectiveness ratio is 15.370 euro 2002. CONCLUSION: The related additional cost seems affordable for an European health care system and justifies the recommendation for its use in the subpopulation overexpressing HER2.

External control in Markovian genetic regulatory networks: the imperfect information case.

Probabilistic Boolean Networks, which form a subclass of Markovian Genetic Regulatory Networks, have been recently introduced as a rule-based paradigm for modeling gene regulatory networks. In an earlier paper, we introduced external control into Markovian Genetic Regulatory networks. More precisely, given a Markovian genetic regulatory network whose state transition probabilities depend on an external (control) variable, a Dynamic Programming-based procedure was developed by which one could choose the sequence of control actions that minimized a given performance index over a finite number of steps. The control algorithm of that paper, however, could be implemented only when one had perfect knowledge of the states of the Markov Chain. This paper presents a control strategy that can be implemented in the imperfect information case, and makes use of the available measurements which are assumed to be probabilistically related to the states of the underlying Markov Chain.