Determinants of Psychosocial Distress in Breast Cancer Patients at a Safety Net Hospital.

INTRODUCTION: Psychosocial distress screening of cancer patients is an American College of Surgeons Commission on Cancer mandate for accredited cancer programs. We evaluated psychosocial distress in breast cancer patients to characterize risk factors for high distress scores at a safety net hospital. MATERIALS AND METHODS: The psychosocial distress screening form includes a list of potential issues and a distress score scaled from 1 through 10. Psychosocial distress screening results were retrospectively analyzed, along with patient demographics and clinical data. Cochran-Mantel-Haenszel test was applied to identify predictors for high distress scores, which were defined as a score of 5 and greater. RESULTS: 775 distress screens were completed by 171 breast cancer patients. High distress scores were reported in 21.3%. Patients who had no evidence of disease at time of screening were less likely to report a high distress score compared to those who were newly diagnosed or in active treatment (odds ratio 0.51, 95% CI, 0.38-0.68, P< .0001). Patients with high distress scores were more likely to report concerns with insurance (29.1% vs. 7.6%, P< .0001), transportation (16.4% vs. 4.6%, P< .0001), housing (15.2% vs 2.1%, P< .0001), sadness/depression (63.6% vs. 14.1, P< .0001), and physical issues (89.1% vs. 52.8%, P< .0001). CONCLUSION: Status of cancer at time of screening, particularly newly diagnosed cancer and active treatment of cancer were associated with high distress scores in this patient group. While there should be an emphasis to ensure patients with these risk factors receive psychosocial distress screening, routine periodic screening for all patients should continue to be implemented to ensure quality cancer care.

Prolonged survival and response to tepotinib in a non-small-cell lung cancer patient with brain metastases harboring MET exon 14 mutation: a research report.

Tyrosine kinase inhibitors (TKIs) have transformed the standard of care in lung cancer. A number of TKIs have been discovered that specifically target oncogenes, including MET receptor tyrosine kinase. Second-generation MET TKIs are showing improved efficacy over first-generation TKIs. Herein, we report a case of a patient with metastatic lung adenocarcinoma harboring a MET exon 14 splice site mutation who has had prolonged disease control by a second-generation MET-TKI tepotinib. A 66-yr-old man was diagnosed with stage IV lung adenocarcinoma. He was started on carboplatin, paclitaxel, and bevacizumab, but had severe toxicity. He was switched to pembrolizumab as his tumor was PD-L1 70%, and molecular testing was not yet performed because of insufficient tissue. A bronchoscopy with endobronchial ultrasound was performed and a MET exon 14 splice site mutation was detected by next-generation sequencing. Upon progression, he was then enrolled in a clinical trial of tepotinib and continues with stable disease for more than 45 cycles and 31 mo. The MET receptor tyrosine kinase and the ligand hepatocyte growth factor (HGF) have been implicated as oncogenes and drivers of non-small-cell lung cancer (NSCLC). Newer MET TKIs including capmatinib and tepotinib more recently showed not only improved localized control and response, but early data suggests intracranial activity as compared to first-generation MET TKIs, both in the front-line and the refractory setting. This is a case report demonstrating an effective duration of response in a patient with widely metastatic lung adenocarcinoma harboring a MET exon 14 mutation.

The Mitochondrion as an Emerging Therapeutic Target in Cancer.

Mitochondria have emerged as important pharmacological targets because of their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis. Furthermore, mitochondria can engage in crosstalk with the tumor microenvironment, and signals from cancer-associated fibroblasts can impinge on mitochondria. Cancer cells can also acquire a hybrid phenotype in which both glycolysis and oxidative phosphorylation (OXPHOS) can be utilized. This hybrid phenotype can facilitate metabolic plasticity of cancer cells more specifically in metastasis and therapy-resistance. In light of the metabolic heterogeneity and plasticity of cancer cells that had until recently remained unappreciated, strategies targeting cancer metabolic dependency appear to be promising in the development of novel and effective cancer therapeutics.

Patient perspectives on ipilimumab across the melanoma treatment trajectory.

PURPOSE: Ipilimumab was the first FDA-approved agent for advanced melanoma to improve survival and represents a paradigm shift in melanoma and cancer treatment. Its unique toxicity profile and kinetics of treatment response raise novel patient education challenges. We assessed patient perceptions of ipilimumab therapy across the treatment trajectory. METHODS: Four patient cohorts were assessed at different time points relative to treatment initiation: (1) prior to initiation of ipilimumab (n = 10), (2) at weeks 10-12 before restaging studies (n = 11), (3) at week 12 following restaging studies indicating progression of disease (n = 10), and (4) at week 12 following restaging studies indicating either a radiographic response or disease stability (n = 10). Patients participated in a semistructured qualitative interview to assess their experiences with ipilimumab. Quality of life was assessed via the Functional Assessment of Cancer Therapy-General and its Melanoma-specific module. RESULTS: Perceived quality of life was comparable across cohorts, and a majority of the sample understood side effects from ipilimumab and the potential for a delayed treatment response. Patients without progression of disease following restaging studies at week 12 held more positive views regarding ipilimumab compared to patients who had progressed. CONCLUSION: Patients generally regarded ipilimumab positively despite the risk of unique toxicities and potential for delayed therapeutic responses; however, those with progression expressed uncertainty regarding whether taking ipilimumab was worthwhile. Physician communication practices and patient education regarding realistic expectations for therapeutic benefit as well as unique toxicities associated with ipilimumab should be developed so that patients can better understand the possible outcomes from treatment.

Impact of AJCC 'T' designation on risk of regional lymph node metastasis in patients with squamous carcinoma of the eyelid.

BACKGROUND/AIMS: Squamous cell carcinoma (SCC) of eyelid is the second most common cancer of the eyelid with the potential for nodal metastasis. The purpose of this report is to determine whether primary tumour size and 'T' designation in the American Joint Committee on Cancer (AJCC) staging system, 7th edition, correlate with the risk of regional nodal metastasis in patients with eyelid SCC. METHODS: Sixty-five consecutive patients with eyelid SCC treated by one ophthalmologist from March 1999 through July 2011 were included in this retrospective cohort study. Disease was staged using the AJCC 7th edition criteria based on clinical, pathological and radiographical data. Main outcome measures included regional lymph node metastasis at presentation, local recurrence, distant metastasis and survival at last follow-up. RESULTS: 40 men and 25 women had a median age of 67.0 years (range 41-89). TNM designations at presentation per the AJCC 7th edition were as follows: T1N0M0, 6 patients; T2aN0M0, 11 patients; T2bN0M0, 17 patients; T2bN1M0, 2 patients; T3aN0M0, 22 patients; T3bN0M0, 2 patients; T3bN1M0, 1 patient; T4N0M0, 3 patients; and T4N1M0, 1 patient. Median follow-up was 27 months (range 1-150). Four patients had nodal metastasis at presentation. Two of these four patients had T2bN1M0 disease, one had T3bN1M0 disease and one had T4N1M0 disease. Two patients, with T3aN0M0 and T4N0M0 tumours, respectively, at presentation, developed lymph node metastasis at 2 weeks and 8.4 months, respectively, after tumour excision. The four patients who had lymph node metastases at presentation and the two who developed lymph node metastases during follow-up had tumours ≥18 mm in greatest dimension or T2b or higher at presentation. Seven local recurrences were observed during follow-up. Two-year and 3-year recurrence-free survival rates were 93% (95% CI 80% to 98%) and 82% (95% CI 63% to 92%), respectively. No distant metastasis or tumour-related death was observed during follow-up. The 2-year and 3-year disease-free survival rates were 90% (95% CI 77% to 96%) and 79% (95% CI 61% to 89%), respectively. CONCLUSIONS: Regional nodal metastases were observed among patients who presented with tumours >T2b. Tumour size and the AJCC TNM designations correlate with metastasis and should be reported more often for eyelid SCCs to allow comparisons across centres.

Cancer risk communication with low health literacy patients: a continuing medical education program.

BACKGROUND: Low health literacy (HL) is an important risk factor for cancer health disparities. OBJECTIVE: Describe a continuing medical education (CME) program to teach primary care physicians (PCP) cancer risk communication and shared decision-making (SDM) with low HL patients and baseline skills assessment. DESIGN: Cluster randomized controlled trial in five primary care clinics in New Orleans, LA. PARTICIPANTS: Eighteen PCPs and 73 low HL patients overdue for cancer screening. INTERVENTION: Primary care physicians completed unannounced standardized patient (SP) encounters at baseline. Intervention physicians received SP verbal feedback; academic detailing to review cancer screening guidelines, red flags for identifying low HL, and strategies for effective counseling; and web-based tutorial of SP comments and checklist items hyperlinked to reference articles/websites. MAIN MEASURES: Baseline PCP self-rated proficiency, SP ratings of physician general cancer risk communication and SDM skills, patient perceived involvement in care. RESULTS: Baseline assessments show physicians rated their proficiency in discussing cancer risks and eliciting patient preference for treatment/decision-making as "very good". SPs rated physician exploration of perceived cancer susceptibility, screening barriers/motivators, checking understanding, explaining screening options and associated risks/benefits, and eliciting preferences for screening as "satisfactory". Clinic patients rated their doctor's facilitation of involvement in care and information exchange as "good". However, they rated their participation in decision-making as "poor". DISCUSSION: The baseline skills assessment suggests a need for physician training in cancer risk communication and shared decision making for patients with low HL. We are determining the effectiveness of teaching methods, required resources and long-term feasibility for a CME program.

WP760, a melanoma selective drug.

PURPOSE: Our goal was to perform studies on the specificity and antimelanoma mechanism of a novel bis-anthracycline, WP760. WP760 initially identified in the NCI 160 screen as anti-melanoma. METHODS: The methyl thiazolyl tetrazolium reduction (MTT) assay was used to test tumor cell growth inhibition; confocal microscopy to view WP760 intracellular distribution; flow cytometry for cell-cycle arrest and apoptosis; and Western blotting was employed to identify and compare quantities and kinetics of cell growth related molecule levels. RESULTS: WP760 induced G(2)/M-phase cell-cycle arrest and apoptosis in melanoma cell lines and short-term melanoma explants established from clinical specimens in a time and concentration dependent manner at nM concentrations. In contrast, effects on fibroblasts and A549 lung cancer cells required higher concentrations, suggesting that WP760 possesses selectivity for melanoma. Molecular studies indicated that WP760 induced p53 stabilization, checkpoint kinase 2 and p27(Kip1) protein upregulation, and activation of caspase-3. Endogenous nitric oxide (NO) production has been implicated in the chemoresistance of melanoma; WP760 caused inhibition of the inducible nitric oxide synthase (iNOS) protein as well as inhibition of phosphorylation of ERK, known to drive the iNOS pathway. Based on WP760 localization into mitochondria, and caspase-3 inhibitor block the killing of WP760, the intrinsic pathway of apoptosis appears to have been activated. CONCLUSIONS: Our results indicate that WP760 affects a critical and unique set of growth regulatory effects in melanoma, and is a promising candidate for further preclinical studies.