Treatment patterns and outcomes among patients diagnosed with unresectable stage III or IV melanoma in Europe: A retrospective,longitudinal survey (MELODY study)

BackgroundMELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal surveY (MELODY), the first multicountry, observational survey in patients with advanced melanoma, aimed to quantify the impact of existing treatment strategies by capturing information on treatment patterns and clinical outcomes.Patients and methodsPatients attending a participating site between 1st July 2005 and 30th June 2006 with ⩾2 months follow-up were eligible. Data were retrieved retrospectively from advanced melanoma diagnosis until 1st May 2008. Treatment data were collected by line of therapy and response and progression-free survival data by line of systemic treatment. Overall survival (OS) was evaluated for all treated patients.ResultsAmong all patients screened, 776 were eligible for this analysis. Median OS from the date of advanced disease diagnosis was 16.4 months. After excluding patients diagnosed prior to 1st July 2005 to account for any bias resulting from patient selection, the 12-month survival rate and median OS from the start date of second-line treatment was 28.8% and 6.8 months, respectively. Survival was lower in patients with brain metastases, elevated lactate dehydrogenase levels and more advanced disease. Rates of complete/partial tumour response were 15% and 7% in patients treated with first- and second-line systemic therapy, respectively.ConclusionsDespite receiving first- and second-line treatment, most patients with advanced melanoma have short survival times and poor prognoses, reinforcing the need for new treatments.     

Hepatitis C Virus (HCV) genotypes distribution among hepatocellular carcinoma patients in Southern Italy: a three year retrospective study

Background

Hepatocellular carcinoma (HCC) is one of the major cause for cancer in the world. Aim of this case-control study was to investigate the distribution pattern of HCV genotypes among HCC patients and suggest whether infection with specific subtypes may be associated with an increased risk of progression to cancer.

Methods

152 HCC anti-HCV positive patients, fulfilling the criteria from the Barcelona 2000 EASL conference, and 568 patients HCV chronically infected but without HCC as control group were included in the study. Serum of each patient was evaluated for viral load estimation and genotyping.

Results

Males with HCC significantly showed to have quite 2 times higher risk of exposure to HCV infection (OR?=?1.72; 95% CI?=?1.15–2.58). Moreover, HCC was significantly associated with older age. In fact, > 50 years older patients showed to have a higher risk of developing HCC (OR?=?17.4; 95% CI?=?4.24 to 71.36) compared to younger patients.HCV RNA rate was significantly higher (83.7%) among HCC patients than in the control group (61.4%, p?<?0.001) and the most prevalent genotype was 1b (68.0% in HCC vs 54.4% in the control group, p?<?0.005). HCC patients significantly have a risk of exposure to HCV 1b infection almost 2 times greater than the control group (OR?=?1.8; 95% CI?=?1.11–2.82). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.65 (1.16–2.33).

Conclusions

Our study detected a significantly higher rate of HCV RNA positivity and a higher rate of HCV 1b infection in HCC patients, suggesting the strict association between subtype 1b infection and HCC. A prospective study with larger number of samples would be needed to confirm our results.

     

Work functioning trajectories in cancer patients: Results from the longitudinal Work Life after Cancer (WOLICA) study

More than 60% of cancer patients are able to work after cancer diagnosis. However, little is known about their functioning at work. Therefore, the aims of this study were to (1) identify work functioning trajectories in the year following return to work (RTW) in cancer patients and (2) examine baseline sociodemographic, health‐related and work‐related variables associated with work functioning trajectories. This longitudinal cohort study included 384 cancer patients who have returned to work after cancer diagnosis. Work functioning was measured at baseline, 3, 6, 9 and 12 months follow‐up. Latent class growth modeling (LCGM) was used to identify work functioning trajectories. Associations of baseline variables with work functioning trajectories were examined using univariate and multivariate analyses. LCGM analyses with cancer patients who completed on at least three time points the Work Role Functioning Questionnaire (n = 324) identified three work functioning trajectories: “persistently high” (16% of the sample), “moderate to high” (54%) and “persistently low” work functioning (32%). Cancer patients with persistently high work functioning had less time between diagnosis and RTW and had less often a changed meaning of work, while cancer patients with persistently low work functioning reported more baseline cognitive symptoms compared to cancer patients in the other trajectories. This knowledge has implications for cancer care and guidance of cancer patients at work.     

Disparities among racial/ethnic groups of patients diagnosed with ependymoma: analyses from the Surveillance,Epidemiology and End Results (SEER) registry

Journal of Neuro-Oncology - Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly arising in infants. Mutations of SWI/SNF chromatin remodeling complex members...     

Phase I-II study of interferon-gamma and eflornithine (DFMO) in patients with advanced renal cell carcinoma, malignant melanoma and colorectal carcinoma

Eflornithine (DFMO) and interferon-gamma (IFN-gamma) are known to exert synergistic activity on inhibition of ornithinedecarboxylase (ODC) in vitro and in experimental animal tumors thereby inhibiting tumor proliferation. In this study, we prospectively investigated therapeutic effects and side effects of a combination of DFMO and IFN-gamma in 15 patients with renal cell carcinoma (RCC), 9 with malignant melanoma (MM), and 9 with colorectal carcinoma (CRC). DEMO was given orally at a dose of 3x4 g/day during the first 2 weeks of each month; IFN-gamma was administered daily subcutaneously during the DFMO administration periods and every other day during the following 2 weeks. The starting dose of IFN-gamma was 30 mu g/m(2) in the first 5 patients and 60 mu g/m(2) in the next 28. IFN-gamma dose was doubled every 4 weeks to a maximum dose of 120 mu g/m(2) and 240 mu g/m(2), respectively. Therapy was applied for three months in cases with stable disease or partial remission. In 15 patients treatment was stopped after 3 to 11 weeks after initiation of therapy because of tumor progression (14 cases) or severe side effects (1 case). In one out of 15 patients with renal cell carcinoma a partial response was observed lasting 7 months, 5 patients showed stable disease, and 9 progressed. In patients with malignant melanoma and colorectal carcinoma, stable disease was observed in one patient and progressive disease in 8 patients per group. The most frequent side effects were fever and gastrointestinal disturbances observed in 26 patients each. The results of this study indicate that DFMO combined with IFN-gamma has no significant therapeutic activity in patients with advanced renal cell carcinoma, malignant melanoma, and colorectal carcinoma.     

Conversion therapy for inoperable advanced gastric cancer patients by docetaxel,cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study

Background

Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes.

Methods

One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m² b.i.d.) on days 1–14 and intravenous cisplatin (60 mg/m²) and docetaxel (50–60 mg/m²) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery.

Results

Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0–88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS.

Conclusions

DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.

     

Chemotherapy treatment patterns,costs, and outcomes of patients with gastric cancer in the United States: a retrospective analysis of electronic medical record (EMR) and administrative claims data

Background

The aim of this study was to conduct a retrospective database analysis to describe the chemotherapy treatment patterns and outcomes of patients with gastric cancer.

Methods

Individuals diagnosed with gastric cancer were identified from the IMS Oncology Database, which contains electronic medical record (EMR) data collected from a variety of community practices, and the Truven Health MarketScan^® Research database, an administrative claims database. Eligible patients were 18 years of age or older and had an ICD-9 code 151.0–151.9. Patients were excluded if they had evidence of cancer within 6 months of the index diagnosis.

Results

There were 5257 eligible patients identified in EMR data: 1982 (37.7 %) of these patients also had data regarding chemotherapy treatments. Of the 1982 patients who received first-line therapy, 42.3 %, 18.1 %, and 7.9 % went on to receive a second, third, and fourth line of chemotherapy, respectively. There were 11891 eligible patients identified in the administrative database; 5299 (44.6 %) had data regarding chemotherapy. Of those initiating chemotherapy, 2888 (54.5 %) received a second line and 1598 (30.2 %) received a third line of treatment. The average total cost of care during first-line therapy was $40,811 [standard deviation (SD) = $49,916], which was incurred over an average of 53.5 (SD = 63.4) days. A similar pattern was evident in second-line treatment (mean/SD, $26,588/$33,301) over 41.2 (SD = 55.7) days.

Conclusions

Costs and duration of care received vary among gastric cancer patients in the U.S. There is a need to understand which regimens may be associated with better health outcomes and to standardize treatment as appropriate.

     

Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain

Objective of this indirect economic comparison was to estimate and compare management costs of grade 3/4 adverse events (AEs) reported for first-line erlotinib or pemetrexed maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC). The economic analysis was performed for Germany, France, Italy and Spain.Types and incidences of reported grade 3/4 AEs observed with erlotinib or pemetrexed maintenance therapy were retrieved from two recently published placebo-controlled trials. Country-specific estimates on standard treatment algorithms and incremental medical resource utilization associated with each of the reported grade 3/4 AEs have been obtained from clinical oncologists practicing in the four countries and co-authoring this article. The resource use items were subsequently assigned country-specific tariffs to estimate total per-patients costs associated with the AE profiles of the two compared maintenance regimens. For the economic analysis a customized economic spreadsheet model was employed.Our comparison shows lower total average per-patient AE management costs for erlotinib than for pemetrexed maintenance therapy in all four studied countries. Total estimated cost savings per patient in favour of erlotinib amount to € 121, € 237, € 106, and € 119 for Germany, France, Italy and Spain, respectively. These AE cost savings for erlotinib when compared to pemetrexed represent a decrease by 80%, 71%, 94%, and 82%, respectively. The study also discovered considerable differences in AE management costs across countries which are primarily due to differences in clinician's estimates of hospitalization referral rates.Erlotinib maintenance therapy in patients with advanced NSCLC causes lower AE management costs than pemetrexed maintenance therapy indicating a potentially superior tolerability profile.     

Women and small cell lung cancer: social characteristics, medical history, management and survival: a retrospective study of all the male and female cases diagnosed in Bas-Rhin (Eastern France) between 1981 and 1994

The literature make it clear that lung cancer in women differs from that in men in several specific aspects. We conducted a retrospective study of the 967 consecutive recorded patients (696 men and 91 women after exclusions) diagnosed with small cell lung cancers (SCLC) between 1981 and 1994 in the Bas-Rhin population-based cancer registry to determine if such particularities could be observed in SCLC. Data included demographic and social characteristics, medical and smoking history, management (diagnosis and treatment), hospitalisation and survival. The end point for survival was 31 December 1998. Women were more frequently single, divorced, or widowed (P=0.007) and lived more often in urban areas (places with more than 10,000 inhabitants) (P=0.017). They differed significantly from men in their tobacco exposure (P=0.0001) and non-smoking rates (P=0.0003) but not in clinical presentation, except for more frequently elevated LDH levels (P=0.02). Bone marrow biopsies were more often performed in men (P=0.004), but management was otherwise comparable. The mean number of hospitalisations (for any reason) was comparable in both sexes but women tended to remain hospitalised longer (P=0.057). Overall survival did not differ, but women older than 70 years died sooner than their male counterparts (P=0.026). Our study confirms that some of gender differences reported in the lung cancer literature exist in SCLC. Sex-related differences in LDH levels have not previously been reported, to our knowledge. North American and European data concerning survival among women and men are discordant. Whether these gender differences are related to a real difference between the sexes or simply to differential exposure to carcinogens remains to be determined.     

Real-world treatment patterns and outcomes of pyrotinib-based therapy in patients with HER2-positive advanced breast cancer (PRETTY): A nationwide,prospective, observational study

Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for treating HER2-positive advanced breast cancer in China. We conducted a nationwide, prospective observational study to examine the real-world data of pyrotinib-based therapy in this population. Patients from 61 sites across China were included. Pyrotinib-based regimens were prescribed at local physician's discretion. Demographics, treatment patterns, prognosis and safety were evaluated. The primary outcome was real-world progression-free survival (rwPFS). Of 1129 patients, pyrotinib-based therapy was prescribed as first-, second- and third- or later-line treatment in 437 (38.7%), 476 (42.2%) and 216 (19.1%) patients, respectively. Median rwPFS (mrwPFS) was 14.3 (95% CI, 13.3-15.2) months in the total population, with the longest mrwPFS of 17.8 (95% CI, 15.2-24.9) months in the first-line setting, followed by 14.4 (95% CI, 12.9-15.3) months in the second-line setting. Patients with third- or later-line treatment also achieved a mrwPFS of 9.3 (95% CI, 8.4-11.8) months. Patients with trastuzumab- or trastuzumab-pertuzumab-treated disease achieved a mrwPFS of 14.3 and 13.6 months, respectively. Dual HER2 blockade with pyrotinib plus trastuzumab showed a mrwPFS of 16.2 months in the total population, with data not mature in the first-line setting. For patients with baseline brain metastases, the mrwPFS was 11.7 months. The most common adverse event was diarrhea (any grade, 73.5%; grade ≥ 3, 15.3%). In real world, pyrotinib-based therapy shows promising effectiveness in the first-, as well as second- and later-line treatment, with acceptable tolerability. Further investigations regarding front-line use or novel combinations of pyrotinib might facilitate to maximize its anti-tumor potential.     

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvantIFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.     

Antimicrobial susceptibility among E. faecalis and E. faecium from France,Germany, Italy,Spain and the UK (T.E.S.T. Surveillance Study, 2004-2009)

Abstract

We report on antimicrobial activity against E. faecalis and E. faecium collected in France, Germany, Italy, Spain, and the UK between 2004 and 2009 as part of the Tigecycline Evaluation and Surveillance Trial (UK in vitro data not included due to low isolate numbers). Overall, 1·1% (n?=?23/2068) of E. faecalis and 11·5% (n?=?103/893) of E. faecium were vancomycin-resistant. High levels of minocycline-resistant E. faecalis were reported in Germany, Spain, France, and Italy (40·2–44·2%); levofloxacin resistance was high in Germany, Italy, and Spain (31·1–41·6%). Minocycline non-susceptibility increased significantly among E. faecalis in Spain and Italy (P<0·001). No tigecycline-resistant E. faecalis were reported. Among E. faecium, resistance ranged from 72·9% (France) to 93·3% (Germany) for ampicillin, from 56·1% (France) to 90·2% (Germany) for levofloxacin, and from 75·3% (Italy) to 94·7% (Germany) for penicillin. Levofloxacin non-susceptibility increased significantly among E. faecium in France and Spain (P<0·001). The lowest rates of antimicrobial resistance among E. faecium were reported for tigecycline (2/893; 0·2%) and linezolid (3/893; 0·3%).     

Fecal incontinence and radiation dose on anal sphincter in patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiotherapy: a retrospective,single-institutional study

Background

The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME.

Methods

We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0–20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V ₂₀, V ₃₀, V ₄₀, V ₅₀, mean dose (D _mean), minimum dose (D _min), D ₉₀ (dose received by 90% of the sphincter) and D ₉₈.

Statistical analysis

The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann–Whitney test.

Results

Mean Wexner score was 5.5 points higher in those patients with V ₂₀ > 0 compared to those for which V ₂₀ = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V ₂₀ on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42.

Conclusions

In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to <20 Gy.

     

Breast Cancer Screening among Low-Income or Uninsured Women: Results from the National Breast and Cervical Cancer Early Detection Pogram, July 1995 to March 2002 (United States)

Objective To describe the results of breast cancer screening among low-income and uninsured women in the only national organized screening program in the US, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Methods We analyzed mammography and diagnostic follow-up data for 789,647 women who received their first mammogram in the NBCCEDP and 454,754 subsequent mammograms among these women. We calculated the rate of mammograms with abnormal findings, diagnostic follow-up, biopsy, and cancers detected per 1000 mammograms by age and racial or ethnic groups. Positive Predictive Values (PPVs) were estimated for abnormal mammograms and biopsy. Results Nearly 64% of the women screened in the program were from 50 to 64 years of age and about 46% were members of racial or ethnic minority groups. Women aged 40 to 49 years had the highest rates of abnormal mammograms and of diagnostic follow-up. However, cancer detection rates were highest in women aged 60 to 64 years. In addition, the PPVs for both abnormal mammograms and biopsy were highest in the oldest age group. Conclusions Cancer detection rates and PPVs for both abnormal mammograms and biopsy were highest in women aged 50 years or more. These results support the programs focus on screening women aged 50 and older for breast cancer.