OBJECTIVE:Preoperative methods to estimate disease-specific survival (DSS) for resectable gastroesophageal (GE) junction and gastric adenocarcinoma are limited. We evaluated the relationship between ...DSS and pretreatment neutrophil to lymphocyte ratio (NLR).
BACKGROUND:The patientʼs inflammatory state is thought to be associated with oncologic outcomes, and NLR has been used as a simple and convenient marker for the systemic inflammatory response. Previous studies have suggested that NLR is associated with cancer-specific outcomes.
METHODS:A retrospective review of a prospectively maintained institutional database was undertaken to identify patients who underwent potentially curative resection for GE junction and gastric adenocarcinoma from 1998 to 2013. Clinicopathologic findings, pretreatment leukocyte values, and follow-up status were recorded. The Kaplan-Meier method was used to estimate DSS, and Cox proportional hazards models were used to evaluate the association between variables and DSS.
RESULTS:We identified 1498 patients who fulfilled our eligibility criteria. Univariate analysis showed that male sex, Caucasian race, increased T and N stage, GE junction location, moderate/poor differentiation, nonintestinal Lauren histology, and vascular and perineural invasion were associated with worse DSS. Elevated NLR was also associated with worse DSS hazard ratio (HR) = 1.11; 95% CI1.08–1.14; P < 0.01. On multivariate analysis, pretreatment NLR as a continuous variable was a highly significant independent predictor of DSS. For every unit increase in NLR, the risk of cancer-associated death increases by approximately 10% (HR = 1.10; 95% CI1.05–1.13; P < 0.0001).
CONCLUSIONS:In patients with resectable GE junction and gastric adenocarcinoma, pretreatment NLR independently predicts DSS. This and other clinical variables can be used in conjunction with cross-sectional imaging and endoscopic ultrasound as part of the preoperative risk stratification process.
Hepatic resection of colorectal liver metastases is associated with long-term survival. This study analyzes actual 10-year survivors after resection of colorectal liver metastases, reports the ...observed rate of cure, and identifies factors that preclude cure.
A single-institution, prospectively maintained database was queried for all initial resections for colorectal liver metastases for the years 1992–2004. Observed cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. Clinical risk score was dichotomized into low (0–2) and high (3–5). Semiparametric proportional hazards mixture cure model was utilized to estimate probability of cure.
We included 1,211 patients with a median follow-up for survivors of 11 years. Median disease-specific survival was 4.9 years (95% CI: 4.4–5.3). 295 patients (24.4%) were actual 10-year survivors. The observed cure rate was 20.6% (n = 250). Among 250 cured patients, 192 (76.8%) had no recurrence and 58 (23.2%) had a resected recurrence with at least 3 years of disease-free follow-up. Extrahepatic disease (n = 88), carcinoembryonic antigen >200 ng/mL (n = 119), positive margin (n = 109), and >10 tumors (n = 31) had observed cure rates less than 10%. In cure model analysis, patients with both extrahepatic disease and high clinical risk score (n = 31) had an estimated probability of cure of 3.5%.
Actual 10-year survival after resection of colorectal liver metastases is 24% with an observed 20% cure rate. Patients with both high clinical risk score and extrahepatic disease have an estimated probability of cure less than 5%. When such factors are identified, strong consideration may be given to preoperative strategies, such as neoadjuvant chemotherapy, to help select patients for surgical therapy.
There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited.
We randomly assigned ...patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival.
Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts.
Clinical benefits were associated with symptom self-reporting during cancer care.
Objectives
This study aims to measure the reproducibility of radiomic features in pancreatic parenchyma and ductal adenocarcinomas (PDAC) in patients who underwent consecutive contrast-enhanced ...computed tomography (CECT) scans.
Methods
In this IRB-approved and HIPAA-compliant retrospective study, 37 pairs of scans from 37 unique patients who underwent CECTs within a 2-week interval were included in the analysis of the reproducibility of features derived from pancreatic parenchyma, and a subset of 18 pairs of scans were further analyzed for the reproducibility of features derived from PDAC. In each patient, pancreatic parenchyma and pancreatic tumor (when present) were manually segmented by two radiologists independently. A total of 266 radiomic features were extracted from the pancreatic parenchyma and tumor region and also the volume and diameter of the tumor. The concordance correlation coefficient (CCC) was calculated to assess feature reproducibility for each patient in three scenarios: (1) different radiologists, same CECT; (2) same radiologist, different CECTs; and (3) different radiologists, different CECTs.
Results
Among pancreatic parenchyma-derived features, using a threshold of CCC > 0.90, 58/266 (21.8%) and 48/266 (18.1%) features met the threshold for scenario 1, 14/266 (5.3%) and 15/266 (5.6%) for scenario 2, and 14/266 (5.3%) and 10/266 (3.8%) for scenario 3. Among pancreatic tumor-derived features, 11/268 (4.1%) and 17/268 (6.3%) features met the threshold for scenario 1, 1/268 (0.4%) and 5/268 (1.9%) features met the threshold for scenario 2, and no features for scenario 3 met the threshold, respectively.
Conclusions
Variations between CECT scans affected radiomic feature reproducibility to a greater extent than variation in segmentation. A smaller number of pancreatic tumor-derived radiomic features were reproducible compared with pancreatic parenchyma-derived radiomic features under the same conditions.
Key Points
• For pancreatic-derived radiomic features from contrast-enhanced CT (CECT), fewer than 25% are reproducible (with a threshold of CCC < 0.9) in a clinical heterogeneous dataset.
• Variations between CECT scans affected the number of reproducible radiomic features to a greater extent than variations in radiologist segmentation.
• A smaller number of pancreatic tumor-derived radiomic features were reproducible compared with pancreatic parenchyma-derived radiomic features under the same conditions.
Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline
or
(g
+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib ...treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g
+ PDAC.
Eligible patients had untreated g
PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m
and gemcitabine 600 mg/m
intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses.
Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B (
= .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B (
= .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months;
= .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months;
= .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia.
Cisplatin and gemcitabine is an effective regimen in advanced g
+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g
/
+ PDAC.
Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly ...used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy.
Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves.
Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line.
Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer.
Addition of trastuzumab to first-line chemotherapy improves overall survival in patients with HER2-positive metastatic gastric cancer. We assessed the safety and activity of pembrolizumab in ...combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric (gastric, oesophageal, or gastroesophageal junction) cancer.
This study was an investigator-initiated, open-label, non-randomised, single-arm, single centre, phase 2 trial in patients aged 18 years or older with HER2-positive metastatic oesophagogastric cancer. Eligible patients had measurable or evaluable non-measurable disease, Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and left ventricular ejection fraction of at least 53%. Patients were eligible to receive an initial induction cycle of 200 mg flat dose of intravenous pembrolizumab and 8 mg/kg loading dose of intravenous trastuzumab. For subsequent cycles, patients received 130 mg/m2 of intravenous oxaliplatin or 80 mg/m2 of cisplatin on day 1, 850 mg/m2 of oral capecitabine twice a day for 2 weeks followed by 1 week off (or intravenous 5-fluorouracil, 800 mg/m2 per day on days 1–5), and a 200 mg flat dose of intravenous pembrolizumab, and 6 mg/kg of trastuzumab, administered on day 1 of each 3-week cycle. The primary endpoint was 6-month progression-free survival, defined as the proportion of patients alive and free of progression at 6 months, assessed in patients who received at least one dose of trastuzumab and pembrolizumab. The regimen would be considered worthy of further investigation if 26 or more of 37 patients were progression-free at 6 months. This trial is registered with ClinicalTrials.gov, NCT02954536, and is ongoing, but closed to enrolment.
Between Nov 11, 2016, and Jan 23, 2019, 37 patients were enrolled. At the time of data cutoff on Aug 6, 2019, median follow-up among survivors was 13·0 months (IQR 11·7–23·5). The primary endpoint was achieved; 26 (70%; 95% CI 54–83) of 37 patients were progression-free at 6 months. The most common treatment-related adverse event of any grade was neuropathy, which was reported in 36 (97%) of 37 patients. The most common grade 3 or 4 adverse events were lymphocytopenia (seven 19% patients with grade 3 and two 5% with grade 4), grade 3 decreased electrolytes (six 16% patients), and grade 3 anaemia (four 11% patients). Serious adverse events occurred in two patients patients (both grade 3 nephritis leading to treatment discontinuation). Four patients discontinued pembrolizumab because of immune-related adverse events. There were no treatment-related deaths.
Pembrolizumab can be safely combined with trastuzumab and chemotherapy and has promising activity in HER2-positive metastatic oesophagogastric cancer. A randomised phase 3 clinical trial assessing the efficacy and safety of pembrolizumab versus placebo in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric cancer is underway.
Merck & Co.
The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose.
We ...evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study).
Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio SIR, 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer-specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively.
Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.
Background
Acral melanoma (AM) is an unusual malignancy with poor survival. This study defines a cohort of patients, treated at a single institution, and the factors associated with survival and ...comparison with nonacral cutaneous melanoma (NACM).
Methods
All patients with AM presenting from 1995 to 2010 were identified from a prospectively maintained database. Analysis of clinicopathologic features of AM associated with disease-specific survival (DSS) was performed. A stratified, stage-matched survival analysis compared the outcome of 281 acral to 843 extremity NACM patients.
Results
A total of 281 AM patients (170 volar, 111 subungual) were identified. Pathologic stage (
p
< 0.001), ulceration (
p
< 0.001), Breslow thickness (
p
< 0.001), and a positive sentinel lymph node (
p
< 0.001) were found to be poor prognostic indicators associated with DSS. In stage-matched analysis, AM had a worse DSS compared with NACM (hazard ratio 1.8; 95 % CI 1.2–2.7;
p
< 0.01).
Conclusions
This study represents the largest, single-institution series describing the characteristics and outcomes of AM. AM tumors exhibit aggressive histopathologic features associated with a poorer survival outcome. AM patients have an inferior survival than extremity NACM when matched for stage, perhaps reflecting inherent alterations in tumor biology. This warrants further investigation into the differences between acral and cutaneous melanoma.
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