Is a Wider Margin (2 cm vs. 1 cm) for a 1.01-2.0 mm Melanoma Necessary?

BACKGROUND: The current NCCN recommendation for resection margins in patients with melanomas between 1.01 and 2 mm deep is a 1-2 cm radial margin. We sought to determine whether margin width had an impact on local recurrence (LR), disease-specific survival (DSS), and type of wound closure. METHODS: Melanomas measuring 1.01-2.0 mm were evaluated at a single institution between 2008 and 2013. All patients had a 1 or 2 cm margin. RESULTS: We identified 965 patients who had a 1 cm (n = 302, 31.3 %) or 2 cm margin (n = 663, 68.7 %). Median age was 64 years, and 592 (61.3 %) were male; 32.5 and 48.7 % of head and neck and extremity patients had a 1 cm margin versus 18.9 % of trunk patients (p < 0.001). LR was 2.0 and  2.1 % for a 1 and 2 cm margin, respectively (p = not significant). Five-year DSS was 87 % for a 1 cm margin and 85 % for a 2 cm margin (p = not significant). Breslow thickness, melanoma on the head and neck, lymphovascular invasion, and sentinel lymph node biopsy (SLNB) status significantly predicted LR on univariate analysis; however, only location and SLNB status were associated with LR on multivariate analysis. Margin width was not significant for LR or DSS. Wider margins were associated with more frequent graft or flap use only on the head and neck (p = 0.025). CONCLUSIONS: Our data show that selectively using a narrower margin of 1 cm did not increase the risk of LR or decrease DSS. Avoiding a 2 cm margin may decrease the need for graft/flap use on the head and neck.

Natural history of polyomaviruses in men: the HPV infection in men (HIM) study.

BACKGROUND: Several new polyomaviruses have been discovered in the last decade, including Merkel cell polyomavirus (MCPyV). Little is known about the natural history of the more recently discovered polyomaviruses. We estimated the incidence, prevalence, and persistence of 9 polyomaviruses (MCPyV, BK polyomavirus, KI polyomavirus, JC polyomavirus, WU polyomavirus, Human polyomavirus 6 [HPyV6], HPyV7, HPyV9, and Trichodysplasia spinulosa-associated polyomavirus) and examined factors associated with MCPyV infection in a prospective cohort of 209 men initially enrolled in the HPV Infection in Men (HIM) study. METHODS: Participants enrolled at the US site of the HIM study were recruited into a substudy of cutaneous viral infections and followed for a median of 12.6 months. Eyebrow hair and normal skin swab specimens were obtained at each study visit, and the viral DNA load was measured using multiplex polymerase chain reaction. RESULTS: MCPyV infection showed the highest prevalence (65.1% of normal skin swab specimens and 30.6% of eyebrow hair specimens), incidence (81.7 cases per 1000 person-months among normal skin swab specimens, and 24.1 cases per 1000 person-months among eyebrow hair specimens), and persistence (85.8% of normal skin swab specimens and 58.9% of eyebrow hair specimens) among all polyomaviruses examined. Age of >44 years (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.03-4.33) and Hispanic race (OR, 2.64; 95% CI, 1.01-6.88) were associated with an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab specimens, respectively. CONCLUSION: MCPyV infection is highly prevalent in adults, with age and race being predisposing factors.

Sentinel lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is indicated for the staging of clinically lymph node-negative melanoma of intermediate thickness, but its use is controversial in patients with thick melanoma. METHODS: From 2002 to 2012, patients with melanoma measuring ≥4 mm in thickness were evaluated at a single institution. Associations between survival and clinicopathologic characteristics were explored. RESULTS: Of 571 patients with melanomas measuring ≥4 mm in thickness and no distant metastases, the median age was 66 years and 401 patients (70.2%) were male. The median Breslow thickness was 6.2 mm; the predominant subtype was nodular (45.4%). SLNB was performed in 412 patients (72%) whereas 46 patients (8.1%) presented with clinically lymph node-positive disease and 113 patients (20%) did not undergo SLNB. A positive SLN was found in 161 of 412 patients (39.1%). For SLNB performed at the study institution, 14 patients with a negative SLNB developed disease recurrence in the mapped lymph node basin (false-negative rate, 12.3%). The median disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) for the entire cohort were 62.1 months, 42.5 months, and 21.2 months, respectively. The DSS and OS for patients with a negative SLNB were 82.4 months and 53.4 months, respectively; 41.2 months and 34.7 months, respectively, for patients with positive SLNB; and 26.8 months and 22 months, respectively, for patients with clinically lymph node-positive disease (P<.0001). The median RFS was 32.4 months for patients who were SLNB negative, 14.3 months for patients who were SLNB positive, and 6.8 months for patients with clinically lymph node-positive disease (P<.0001). CONCLUSIONS: With an acceptably low false-negative rate, patients with thick melanoma and a negative SLNB appear to have significantly prolonged RFS, DSS, and OS compared with those with a positive SLNB. Therefore, SLNB should be considered as indicated for patients with thick, clinically lymph node-negative melanoma.

Resection of residual disease after isolated limb infusion (ILI) is equivalent to a complete response after ILI-alone in advanced extremity melanoma.

BACKGROUND: Isolated limb infusion (ILI) is a limb-preserving treatment for in-transit extremity melanoma. The benefit of resecting residual disease after ILI is unclear. METHODS: A multi-institutional experience was analyzed comparing patients who underwent ILI plus resection of residual disease (ILI + RES) versus ILI-alone. RESULTS: A total of 176 patients were included, 154 with ILI-alone and 22 with ILI + RES. There were no differences between the groups with respect to gender, age, extremity affected, or time from diagnosis to ILI. All surgical resections were performed as an outpatient procedure, separate from the ILI. Within the ILI + RES group, 15 (68%) had a partial response (PR), 2 (9%) stable disease (SD), and 5 (23%) progressive disease (PD). The ILI-alone group had 52 (34%) CR, 30 (19%) PR, 15 (10%) SD, and 46 (30%) PD. Eleven (7%) ILI-alone patients did not have 3-month response available for review. Evaluating overall survival (OS) from date of ILI, the ILI-alone group had a median OS of 30.9 months, whereas the ILI + RES group had not reached median OS, p = 0.304. Although the ILI + RES group had a slightly longer disease-free survival (DFS) compared to those with a CR after ILI-alone (12.4 vs. 9.6), this was not statistically significant, p = 0.978. Within the ILI + RES group, those with an initial PR after ILI had improved DFS versus those with SD or PD after ILI, p < 0.0001. CONCLUSIONS: Resection of residual disease after ILI offers a DFS and OS similar to those who have a CR after ILI-alone. It may offer a treatment strategy that benefits patients undergoing ILI.

Primary care utilization and colorectal cancer incidence and mortality among Medicare beneficiaries: a population-based, case-control study.

BACKGROUND: Utilization of primary care may decrease colorectal cancer (CRC) incidence and death through greater receipt of CRC screening tests. OBJECTIVE: To examine the association of primary care utilization with CRC incidence, CRC deaths, and all-cause mortality. DESIGN: Population-based, case-control study. SETTING: Medicare program. PARTICIPANTS: Persons aged 67 to 85 years diagnosed with CRC between 1994 and 2005 in U.S. Surveillance, Epidemiology, and End Results (SEER) regions matched with control patients (n = 205,804 for CRC incidence, 54,160 for CRC mortality, and 121,070 for all-cause mortality). MEASUREMENTS: Primary care visits in the 4- to 27-month period before CRC diagnosis, CRC incidence, CRC mortality, and all-cause mortality. RESULTS: Compared with persons having 0 or 1 primary care visit, persons with 5 to 10 visits had lower CRC incidence (adjusted odds ratio [OR], 0.94 [95% CI, 0.91 to 0.96]) and mortality (adjusted OR, 0.78 [CI, 0.75 to 0.82]) and lower all-cause mortality (adjusted OR, 0.79 [CI, 0.76 to 0.82]). Associations were stronger in patients with late-stage CRC diagnosis, distal lesions, and diagnosis in more recent years when there was greater Medicare screening coverage. Ever receipt of CRC screening and polypectomy mediated the association of primary care utilization with CRC incidence. LIMITATION: This study used administrative data, which made it difficult to identify potential confounders and prevented examination of the content of primary care visits. CONCLUSION: Medicare beneficiaries with higher utilization of primary care have lower CRC incidence and mortality and lower overall mortality. Increasing and promoting access to primary care in the United States for Medicare beneficiaries may help decrease the national burden of CRC. PRIMARY FUNDING SOURCE: American Cancer Society.

The effects of primary care on breast cancer mortality and incidence among Medicare beneficiaries.

BACKGROUND: Primary care physician (PCP) services may have an impact on breast cancer mortality and incidence, possibly through greater use of screening mammography. METHODS: The authors conducted a retrospective, 1:1 matching case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database to examine use of PCP services and their association with breast cancer mortality and incidence. SEER cases representing the 3 outcomes of interest (breast cancer mortality, all-cause mortality among women diagnosed with breast cancer, and breast cancer incidence) were matched to unaffected controls from the 5% Medicare random sample. Conditional logistic regression was used to examine associations between physician visits and breast cancer outcomes while controlling for other covariates. RESULTS: Women who had 2 or more PCP visits during the 24-month assessment interval had lower odds of breast cancer mortality, all-cause mortality, and late-stage breast cancer diagnosis compared with women who had no PCP visits or 1 PCP visit while adjusting for other covariates, including mammography and non-PCP visits. Women who had 5 to 10 PCP visits had 0.69 times the odds of breast cancer mortality (95% confidence interval, 0.63-0.75), 0.83 times the odds of death from any cause having been diagnosed with breast cancer (95% confidence interval, 0.79-0.87), and 0.67 times the odds of a late-stage breast cancer diagnosis (95% confidence interval, 0.61-0.73) compared with those who had no PCP visits or 1 PCP visit. CONCLUSIONS: The current findings suggest that PCPs play an important role in reducing breast cancer mortality among the Medicare population. Further research is needed to better understand the impact of primary care on breast cancer and other cancers that are amendable to prevention or early detection.

Isolated limb infusion in a series of over 100 infusions: a single-center experience.

BACKGROUND: Isolated limb infusion (ILI) is a therapeutic option for patients with recurrent, unresectable extremity malignancies. METHODS: A prospectively collected single-institution database of patients undergoing ILI was analyzed for preoperative, intraoperative, and postoperative parameters and outcomes. RESULTS: From May 2007 to January 2012, a total of 76 patients successfully underwent initial ILI, and 28 after either previous hyperthermic isolated limb perfusion or ILI. Seventy-nine patients (74 %) had melanoma, 24 (22 %) sarcoma, 3 (3 %) Merkel cell, and 1 (1 %) squamous cell carcinoma. There were 55 (72 %) initial and 22 (79 %) repeat lower extremity (LE) ILIs, and 21 (78 %) initial and 6 (22 %) repeat upper extremity (UE) ILIs. Serologic toxicity, measured by serum creatine kinase (CK), peaked higher and later in LE ILIs, median 620 versus 124 IU/L, and postoperative day 4 versus 2, respectively (P < 0.05). LE ILIs had a longer hospital length of stay (LOS), median 6 versus 5 days (P < 0.0001). A median grade II Wieberdink regional toxicity was observed. Three-month follow-up was available in 94 (90 %). A response (overall response rate, ORR) was seen in 72 % of ILIs performed for melanoma and 58 % for sarcoma. No difference in response was observed between UE versus LE or between initial versus repeat ILIs. Repeat UE ILIs, however, appeared to have an improved ORR than repeat LE ILIs, 83 versus 64 %. CONCLUSIONS: ILI may be successfully performed for cutaneous and soft tissue malignancies. LE ILIs have higher CK levels and slightly longer LOS. Repeat ILIs are not associated with increased toxicity and similar ORR. UE ILIs may have better ORR.

Feasibility trial of a Spanish-language multimedia educational intervention.

BACKGROUND: Hispanic cancer patients are underrepresented in clinical trials; research suggests lack of knowledge and language barriers contribute to low accrual. Multimedia materials offer advantages to Hispanic populations because they have high acceptability, are easy to disseminate, and can be viewed with family. PURPOSE: Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish-language multimedia intervention to educate Hispanic cancer patients about clinical trials. We explored the feasibility of delivering the intervention in medical oncology clinics. METHODS: A total of 35 patients were randomized to either the multimedia intervention group (n = 18) or a control group (n = 17) who were asked to read the National Cancer Institute's Spanish-language clinical trials brochure. Self-reported data on knowledge about and attitudes toward clinical trials, self-efficacy for participating in a clinical trial, intention to participate in a clinical trial if asked, and receptivity to information about a clinical trial were collected at baseline and 10 days later. RESULTS: Delivery of the multimedia presentation in oncology clinics was feasible. The intervention group had more knowledge about clinical trials at follow-up than the control group; scores for intention to participate in a clinical trial by participants in the intervention group increased from 3.8 to 4.0 of a possible 5, but declined in the control group from 4.5 to 4.1. No statistically significant difference was detected between groups in scores for attitudes or self-efficacy for making a decision to participate in a clinical trial. LIMITATIONS: Our sample size was inadequate to identify differences between the informational methods. Although all patients were asked about their willingness to participate in a clinical trial, this decision was hypothetical. In addition, the study was conducted with a sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other Hispanic populations. CONCLUSION: In the pilot project, we demonstrated the feasibility of delivering multimedia information to patients in medical oncology clinics. Because delivery in a clinical setting was found to be feasible, a larger study should be conducted to evaluate the efficacy of the multimedia intervention with respect to promoting accrual of Hispanic patients to clinical trials.

Merkel cell carcinoma of unknown primary origin.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. METHODS: After institutional review board approval, our institutional database spanning the years 1998-2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. RESULTS: From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. CONCLUSIONS: Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients.

Influence of primary care on breast cancer outcomes among Medicare beneficiaries.

PURPOSE: We used the Surveillance Epidemiology and End Results (SEER)-Medicare database to explore the association between primary care and breast cancer outcomes. METHODS: Using a retrospective cohort study of 105,105 female Medicare beneficiaries with a diagnosis of breast cancer in SEER registries during the years 1994-2005, we examined the total number of office visits to primary care physicians and non-primary care physicians in a 24-month period before cancer diagnosis. For women with invasive cancers, we examined the odds of diagnosis of late-stage disease, according to the American Joint Commission on Cancer (AJCC) (stages III and IV vs stages I and II), and survival (breast cancer specific and all cause) using logistic regression and proportional hazards models, respectively. We also explored whether including noninvasive cancers, such as ductal carcinoma in situ (DCIS), would alter results and whether prior mammography was a potential mediator of associations. RESULTS: Primary care physician visits were associated with improved breast cancer outcomes, including greater use of mammography, reduced odds of late-stage diagnosis, and lower breast cancer and overall mortality. Prior mammography (and resultant earlier stage diagnosis) mediated these associations in part, but not completely. Similar results were seen for non-primary care physician visits. Results were similar when women with DCIS were included in the analysis. CONCLUSIONS: Medicare beneficiaries with breast cancer had better outcomes if they made greater use of a primary care physician's ambulatory services. These findings suggest adequate primary medical care may be an important factor in achieving optimal breast cancer outcomes.

Multiplexed Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry Quantification of Cancer Signaling Proteins.

Quantitative evaluation of protein expression across multiple cancer-related signaling pathways (e.g., Wnt/ß-catenin, TGF-ß, receptor tyrosine kinases (RTK), MAP kinases, NF-κB, and apoptosis) in tumor tissues may enable the development of a molecular profile for each individual tumor that can aid in the selection of appropriate targeted cancer therapies. Here, we describe the development of a broadly applicable protocol to develop and implement quantitative mass spectrometry assays using cell line models and frozen tissue specimens from colon cancer patients. Cell lines are used to develop peptide-based assays for protein quantification, which are incorporated into a method based on SDS-PAGE protein fractionation, in-gel digestion, and liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM/MS). This analytical platform is then applied to frozen tumor tissues. This protocol can be broadly applied to the study of human disease using multiplexed LC-MRM assays.

Prevalence and concordance of human papillomavirus infection at multiple anatomic sites among HIV-infected women from Chennai, India.

Human papillomavirus (HPV) infection at the cervix, anus and oropharynx has been rarely concurrently estimated among HIV-infected women. Using multiplex polymerase chain reaction testing, we prospectively evaluated HPV genotype distribution across three anatomic sites among 50 eligible HIV-infected women from Chennai, India, who provided biological specimens and answered a sexual behaviour questionnaire. We also assessed clinical and behavioural factors related to HPV prevalence. Oncogenic HPV prevalence was comparable between the anus and cervix at 52.2% and 52.0% and lower at the oropharynx at 13.2%; 78% of women with a cervical HPV infection had the same type in the anus. Newly acquired oncogenic HPV infections were lower at cervix (24%) than anus (35%) at three months. 'Any type' cervical HPV prevalence was higher among women with low education and less than five years since HIV diagnosis. CD4+ count and antiretroviral therapy status were not associated with HPV prevalence at the three anatomic sites; however, enrolment cervical HPV16 prevalence was elevated among women with nadir CD4+ <200 cells/µL and enrolment CD4+ <350 cells/µL. Regular cervical screening is essential in HIV-infected Indian women irrespective of CD4+ count and antiretroviral therapy status. Additional research clarifying the natural history of anal HPV infection is also needed in this population.

Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma.

PURPOSE: The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. EXPERIMENTAL DESIGN: HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1 mg/kg, 3 mg/kg, or 10 mg/kg i.v.) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse-free survival (RFS), overall survival (OS), and immunologic correlative studies. RESULTS: Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events [hypokalemia (1), rash (1), enteritis (1), and colitis (2)] were observed. Ten of 33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4(+)/CD4(+), CD25(+)Treg/CD4(+), and tetramer specific CD8(+) T-cell populations were observed with treatment (P < 0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25(+)Treg/CD4(+) populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. CONCLUSIONS: Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study.

Natural history of cutaneous human papillomavirus (HPV) infection in men: the HIM study.

Accumulating evidence suggests that cutaneous human papillomavirus (HPV) infection is associated with non-melanoma skin cancer (NMSC). Little is known about the natural history of cutaneous HPV. A sub-cohort of 209 men with no NMSC history, initially enrolled in the HPV infection in men (HIM) study, were followed for a median of 12.6 months. Epidemiological data were collected through self-administered questionnaires. Cutaneous HPV DNA was measured in normal skin swabs (SS) and eyebrow hairs (EB) for 25 and 16 HPV types in genera ß and γ, respectively. Any ß HPV infection was more prevalent in SS (67.3%) compared to EB (56.5%, p = 0.04). Incidence in SS was higher than 20 per 1,000 person-months for HPV types 4, 5, 23, 38 and 76. Median duration of persistence of ß and γ HPV infection was 8.6 and 6.1 months in EB, respectively, and 11.3 months and 6.3 months, in SS, respectively. Older age (>44 years vs. 18-30 years) was significantly associated with prevalent (SS OR = 3.0, 95% CI = 1.2-7.0) and persistent ß HPV infection (EB OR = 6.1, 95% CI = 2.6-14.1). History of blistering sunburn was associated with prevalent (OR = 2.8, 95% CI = 1.3-5.8) and persistent (OR = 2.3, 95% CI = 1.2-4.6) ß HPV infection in SS. Cutaneous HPV is highly prevalent in men, with age and blistering sunburn being significant risk factors for cutaneous ß HPV infection.

Tyrosine phosphoproteomics identifies both codrivers and cotargeting strategies for T790M-related EGFR-TKI resistance in non-small cell lung cancer.

PURPOSE: Irreversible EGFR-tyrosine kinase inhibitors (TKI) are thought to be one strategy to overcome EGFR-TKI resistance induced by T790M gatekeeper mutations in non-small cell lung cancer (NSCLC), yet they display limited clinical efficacy. We hypothesized that additional resistance mechanisms that cooperate with T790M could be identified by profiling tyrosine phosphorylation in NSCLC cells with acquired resistance to reversible EGFR-TKI and harboring T790M. EXPERIMENTAL DESIGN: We profiled PC9 cells with TKI-sensitive EGFR mutation and paired EGFR-TKI-resistant PC9GR (gefitinib-resistant) cells with T790M using immunoaffinity purification of tyrosine-phosphorylated peptides and mass spectrometry-based identification/quantification. Profiles of erlotinib perturbations were examined. RESULTS: We observed a large fraction of the tyrosine phosphoproteome was more abundant in PC9- and PC9GR-erlotinib-treated cells, including phosphopeptides corresponding to MET, IGF, and AXL signaling. Activation of these receptor tyrosine kinases by growth factors could protect PC9GR cells against the irreversible EGFR-TKI afatinib. We identified a Src family kinase (SFK) network as EGFR-independent and confirmed that neither erlotinib nor afatinib affected Src phosphorylation at the activation site. The SFK inhibitor dasatinib plus afatinib abolished Src phosphorylation and completely suppressed downstream phosphorylated Akt and Erk. Dasatinib further enhanced antitumor activity of afatinib or T790M-selective EGFR-TKI (WZ4006) in proliferation and apoptosis assays in multiple NSCLC cell lines with T790M-mediated resistance. This translated into tumor regression in PC9GR xenograft studies with combined afatinib and dasatinib. CONCLUSIONS: Our results identified both codrivers of resistance along with T790M and support further studies of irreversible or T790M-selective EGFR inhibitors combined with dasatinib in patients with NSCLC with acquired T790M.

The influence of dermatologist and primary care physician visits on melanoma outcomes among Medicare beneficiaries.

BACKGROUND: Ambulatory visits to dermatologists and primary care physicians (PCPs) may improve melanoma outcomes through early detection. We sought to measure the effect of dermatologist and PCP visits on melanoma stage at diagnosis and mortality. METHODS: We used data from the database linking Surveillance Epidemiology and End Results (SEER) and Medicare data (1994 to 2005) to examine patterns of dermatologist and PCP ambulatory visits before diagnosis for 18,884 Medicare beneficiaries with invasive melanoma or unknown stage at diagnosis. Visits were assessed during the 2-year time interval before the month of diagnosis. We examined whether dermatologist and PCP visits were associated with diagnosis of thinner melanomas (defined as local stage tumors having Breslow thickness <1 mm) and lower melanoma mortality. RESULTS: Medicare beneficiaries visiting both a dermatologist and PCP before diagnosis had greater odds of diagnosis of a thin melanoma (adjusted odds ratio, 1.26; 95% confidence interval, 1.12-1.41) and lower melanoma mortality (adjusted hazard ratio 0.66, 95% confidence interval, 0.57-0.76) compared with those without such visits. The mortality findings were attenuated once stage at diagnosis was adjusted for in the multivariable model. CONCLUSION: Improved melanoma outcomes among Medicare beneficiaries may depend on adequate access and use of dermatologist and PCP services.