A Phase I Trial of VEGF-A Inhibition Combined with PD-L1 Blockade for Recurrent Glioblastoma.

Purpose: The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy. Patient and Methods: Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells. Results: A total of 12 patients (median age 64; range, 37-73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4-16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5-4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival. Conclusions: Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease. Significance: Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.

Quality Care in Survivorship: Lessons Learned From the ASCO Quality Oncology Practice Initiative.

PURPOSE: The ASCO Quality Oncology Practice Initiative (QOPI) project was established to evaluate the influence of guideline recommendations on routine clinical practice. METHODS: QOPI provided summary data from 839 unique practices in which data were collected every six months from the Fall of 2015 to the Spring of 2019. From these data, six items were chosen based on their relationship to domains of survivorship. A zero-inflated negative binomial regression model was used to test for trends in QOPI measures adherence rates over time. The models were adjusted for the time period, region, practice-ownership, multispecialty site, fellowship program, and hospital type. RESULTS: Smoking cessation counseling recommended and smoking cessation counseling administered or referred both increased over time, 50%-61% (adjusted incidence rate ratios (IRR), 1.028; 95% CI, 1.016 to 1.040; P < .001) and 34%-49% (adjusted IRR, 1.052; 95% CI, 1.035 to 1.070; P < .001), respectively. Infertility risks discussed before chemotherapy increased from 36% to 53% (adjusted IRR, 1.056; 95% CI, 1.035 to 1.078; P < .001) and fertility options discussed or referred to specialists increased from 23% to 38% (adjusted IRR, 1.074; 95% CI, 1.046 to 1.102; P < .001). Twenty-nine percent documented a positron emission tomography, computed tomography, or bone scan within the first 12 months for women diagnosed with early breast cancer treated for curative intent (adjusted IRR, 1.000; 95% CI, 0.977 to 1.024; P = .971). Tumor marker surveillance within 12 months increased from 78% to 87% (adjusted IRR, 1.018; 95% CI, 1.002 to 1.033; P = .023). CONCLUSION: As scientific evidence to guide cancer survivorship care grows, the role of guideline recommendations permeating clinical practice using quality metrics will become increasingly important.

Combined Vaccination with NY-ESO-1 Protein, Poly-ICLC, and Montanide Improves Humoral and Cellular Immune Responses in Patients with High-Risk Melanoma.

Given its ability to induce both humoral and cellular immune responses, NY-ESO-1 has been considered a suitable antigen for a cancer vaccine. Despite promising results from early-phase clinical studies in patients with melanoma, NY-ESO-1 vaccine immunotherapy has not been widely investigated in larger trials; consequently, many questions remain as to the optimal vaccine formulation, predictive biomarkers, and sequencing and timing of vaccines in melanoma treatment. We conducted an adjuvant phase I/II clinical trial in high-risk resected melanoma to optimize the delivery of poly-ICLC, a TLR-3/MDA-5 agonist, as a component of vaccine formulation. A phase I dose-escalation part was undertaken to identify the MTD of poly-ICLC administered in combination with NY-ESO-1 and montanide. This was followed by a randomized phase II part investigating the MTD of poly-ICLC with NY-ESO-1 with or without montanide. The vaccine regimens were generally well tolerated, with no treatment-related grade 3/4 adverse events. Both regimens induced integrated NY-ESO-1-specific CD4+ T-cell and humoral responses. CD8+ T-cell responses were mainly detected in patients receiving montanide. T-cell avidity toward NY-ESO-1 peptides was higher in patients vaccinated with montanide. In conclusion, NY-ESO-1 protein in combination with poly-ICLC is safe, well tolerated, and capable of inducing integrated antibody and CD4+ T-cell responses in most patients. Combination with montanide enhances antigen-specific T-cell avidity and CD8+ T-cell cross-priming in a fraction of patients, indicating that montanide contributes to the induction of specific CD8+ T-cell responses to NY-ESO-1.

Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial.

Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and trigger natural killer cells to kill tumor cells.Patients and Methods: In this pilot study, eligible patients included those with recurrent metastatic disease in whom prior systemic therapy (head and neck squamous cell cancer and melanoma) failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly-ICLC 3× weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM) boosters biweekly for 7 weeks, with a 1-week rest period. Immune response was evaluated by immunohistochemistry (IHC) and RNA sequencing (RNA-seq) in tumor and blood.Results: Two patients completed 2 cycles of IT treatments, and 1 achieved clinical benefit (stable disease, progression-free survival 6 months), whereas the remainder had progressive disease. Poly-ICLC was well tolerated, with principal side effects of fatigue and inflammation at injection site (

Laparoscopic Assessment to Determine the Likelihood of Achieving Optimal Cytoreduction in Patients Undergoing Primary Debulking Surgery for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of laparoscopic assessment to determine the likelihood of achieving optimal cytoreduction (OC) in patients undergoing primary debulking surgery (PDS) for ovarian cancer. METHODS: All patients who underwent diagnostic laparoscopy and PDS at our institution from January 2008 to December 2013 were identified. We determined the likelihood of achieving optimal cytoreduction by laparoscopic assessment based on tumor site, pattern of spread, and disease burden. Sensitivity was defined as the number of patients who achieved optimal cytoreduction after laparoscopic assessment divided by the number of patients with disease deemed resectable by laparoscopy. RESULTS: We identified 55 patients during study period. Twenty-one of the 55 patients (38%) were early stage disease. Six (10.9%) patients had disease deemed unresectable and 49 (89.1%) had disease deemed resectable at the time of laparoscopy. OC was achieved in 48 of 49 (97.9%) patients. The sensitivity of laparoscopy in predicting OC was 98% (95% confidence interval, 89.3%-99.9%). The operation was completed laparoscopically in 23 of 49 patients (47%); in 26 of 49 (53%), PDS was performed by laparotomy. There were no port site metastases reported. The rate of postoperative complications was 16%. With a median follow-up of 30 months, the median overall survival was not reached and the 75th percentile for overall survival was 37 months. CONCLUSIONS: Laparoscopy was shown to have a high sensitivity in predicting OC and is a feasible tool in triaging patients with ovarian cancer. Laparoscopy is not associated with adverse surgical outcomes.

Patient-derived Interstitial Fluids and Predisposition to Aggressive Sporadic Breast Cancer through Collagen Remodeling and Inactivation of p53.

Purpose: Despite the fact that interstitial fluid (IF) represents a third of our body fluid, it is the most poorly understood body fluid in medicine. Increased IF pressure is thought to result from the increased deposition of extracellular matrix in the affected tissue preventing its reabsorption. In the cancer field, increased rigidity surrounding a cancerous mass remains the main reason that palpation and radiologic examination, such as mammography, are used for cancer detection. While the pressure produced by IF has been considered, the biochemical composition of IF has not been considered in its effect on tumors.Experimental Design: We classified 135 IF samples from bilateral mastectomy patients based on their ability to promote the invasion of breast cancer cells.Results: We observed a wide range of invasion scores. Patients with high-grade primary tumors at diagnosis had higher IF invasion scores. In mice, injections of high-score IF (IFHigh) in a normal mammary gland promotes ductal hyperplasia, increased collagen deposition, and local invasion. In a mouse model of residual disease, IFHigh increased disease progression and promoted aggressive visceral metastases. Mechanistically, we found that IFHigh induces myofibroblast differentiation and collagen production through activation of CLIC4. IFHigh also downregulates RYBP, leading to degradation of p53. Furthermore, in mammary glands of heterozygous p53-mutant knock-in mice, IFHigh promotes spontaneous tumor formation.Conclusions: Our study indicates that IF can increase the deposition of extracellular matrix and raises the provocative possibility that they play an active role in the predisposition, development, and clinical course of sporadic breast cancers. Clin Cancer Res; 23(18); 5446-59. ©2017 AACR.

Changes in Pathological Complete Response Rates after Neoadjuvant Chemotherapy for Breast Carcinoma over Five Years.

Historically, neoadjuvant chemotherapy (NACT) was extrapolated from adjuvant regimens. Dual HER2 blockade and the introduction of carboplatin for triple negative breast cancers (TNBC) emerged by December 2013 and have improved pathological complete response (pCR) rates. The objective of this study was to assess the pCR rates before and after the introduction of these new neoadjuvant regimens. Materials and Methods. Stage I-III breast cancer patients who received NACT were analyzed for rates of pCR by clinical characteristics (i.e., age, BMI, axillary lymphadenopathy, and histologic subtype), by time period (1 = 3/2010-11/2013, 2 = 12/2013-3/2015), and by type of chemotherapy (e.g., anthracycline/taxane only, carboplatin-containing, and HER2 blockade). Results. 113 patients received NACT. Overall pCR rate was 26.5 percent (n = 30). The pCR rate increased from 14% to 43.1% (p = 0.001) from time period 1 to time period 2 and were associated with HER2 positivity (p = 0.003), receiving treatment during time period 2 (p = 0.001) and using an anthracycline/taxane plus additional agent type of regimen (p = 0.004). Conclusions. Our study revealed a significant difference in rates of pCR over five years. Window of opportunity trials and other trials that utilize pCR analysis should be encouraged.

Decision-Making in Breast Cancer Surgery: Where Do Patients Go for Information?

Patient decision-making regarding breast cancer surgery is multifactorial, and patients derive information on surgical treatment options from a variety of sources which may have an impact on choice of surgery. We investigated the role of different information sources in patient decision-making regarding breast cancer surgery. Two hundred and sixty-eight patients with breast cancer, eligible for breast-conserving therapy were surveyed in the immediate preoperative period, and clinical data were also collected. This survey evaluated the scope and features of patient-driven research regarding their ultimate choice of surgical treatment. The two most common sources of information used by patients were written material from surgeons (199/268-74%) and the Internet (184/268-69%). There was a trend for women who chose bilateral mastectomy to use the Internet more frequently than those choosing unilateral mastectomy (P = 0.056). Number of surgeons consulted, genetic testing, and MRI were significant predictors of patient choice of mastectomy over breast-conserving therapy. Multivariate analysis showed that the number of surgeons consulted (P < 0.001) and genetic testing (P < 0.001) were independent predictors of choosing mastectomy, whereas MRI was not. In conclusions, understanding factors driving patient decision-making may promote more effective education for patients requiring breast cancer surgery.

Lactation opposes pappalysin-1-driven pregnancy-associated breast cancer.

Pregnancy is associated with a transient increase in risk for breast cancer. However, the mechanism underlying pregnancy-associated breast cancer (PABC) is poorly understood. Here, we identify the protease pappalysin-1 (PAPP-A) as a pregnancy-dependent oncogene. Transgenic expression of PAPP-A in the mouse mammary gland during pregnancy and involution promotes the deposition of collagen. We demonstrate that collagen facilitates the proteolysis of IGFBP-4 and IGFBP-5 by PAPP-A, resulting in increased proliferative signaling during gestation and a delayed involution. However, while studying the effect of lactation, we found that although PAPP-A transgenic mice lactating for an extended period of time do not develop mammary tumors, those that lactate for a short period develop mammary tumors characterized by a tumor-associated collagen signature (TACS-3). Mechanistically, we found that the protective effect of lactation is associated with the expression of inhibitors of PAPP-A, STC1, and STC2. Collectively, these results identify PAPP-A as a pregnancy-dependent oncogene while also showing that extended lactation is protective against PAPP-A-mediated carcinogenesis. Our results offer the first mechanism that explains the link between breast cancer, pregnancy, and breastfeeding.

Early Childhood Adversity and its Associations With Anxiety, Depression, and Distress in Women With Breast Cancer.

BACKGROUND: Certain vulnerability factors have been found to place patients at risk for depression and anxiety, especially within the context of medical illness. OBJECTIVES: We sought to describe the relationships among early childhood adversity (ECA) and anxiety, depression and distress in patients with breast cancer. METHODS: Patients with breast cancer (stages 0-IV) were assessed for ECA (i.e., the Risky Families Questionnaire subscales include Abuse/Neglect/Chaotic Home Environment), distress (i.e., Distress Thermometer and Problem List), anxiety (Hospital Anxiety and Depression Scale-Anxiety), depression (Hospital Anxiety and Depression Scale-Depression), meeting standardized cut-off thresholds for distress (Distress Thermometer and Problem List ≥4 or ≥7)/anxiety (Hospital Anxiety and Depression Scale-Anxiety ≥8)/depression (Hospital Anxiety and Depression Scale-Depression ≥8) and demographic factors. RESULTS: A total of 125 participants completed the study (78% response rate). ECA was associated with depression (p <0.001), anxiety (p = 0.001), and distress (p = 0.006), meeting cut-off threshold criteria for distress (p = 0.024), anxiety (p = 0.048), and depression (p = 0.001). On multivariate analysis, only depression (p = 0.04) and emotional issues (i.e., component of Distress Thermometer and Problem List) (p = 0.001) were associated with ECA. Neglect, but not Abuse and Chaotic Home Environment, was associated with depression (ß = 0.442, p < 0.001), anxiety (ß = 0.342, p = 0.002), and self-identified problems with family (ß = 0.288, p = 0.022), emotion (ß = 0.345, p = 0.004), and physical issues (ß = 0.408, p < 0.001). CONCLUSION: ECA and neglect are associated with multiple psychologic symptoms, but most specifically depression in the setting of breast cancer. ECA contributes to psychologic burden as a vulnerability factor. ECA may help to explain individual patient trajectories and influence the provision of patient-centered care for psychologic symptoms in patients with breast cancer.

ReCAP: Would Women With Breast Cancer Prefer to Receive an Antidepressant for Anxiety or Depression From Their Oncologist?

PURPOSE: Patient treatment preferences for the management of anxiety and depression influence adherence to treatment and treatment outcomes, yet the preferences of patients with breast cancer for provider-specific pharmacologic management of anxiety and depression is unknown. This study examined the antidepressant prescriber preferences of patients with breast cancer and their preferences for treatment by a mental health professional. METHODS: Patients with breast cancer (stages 0 to IV) were asked two questions: "Would you be willing to have your oncologist treat your depression or anxiety with an antidepressant medication if you were to become depressed or anxious at any point during your treatment?" and "Would you prefer to be treated by a psychiatrist or mental health professional for problems with either anxiety or depression?" In addition, the Distress Thermometer and Problem List, Hospital Anxiety and Depression Scale, Risky Families Questionnaire, and demographic information were assessed. RESULTS: One hundred twenty-five participants completed the study. A total of 60.4% were willing to accept an antidepressant from an oncologist, and 26.3% preferred treatment by a mental health professional. The 77.3% who were willing to receive an antidepressant from their oncologist reported either no preference or that treatment by a mental health professional did not matter (P = .01). Participants taking antidepressants (P = .02) or reporting high chronic stress (P = .03) preferred a mental health professional. CONCLUSION: The majority of patients accepted antidepressant prescribing by their oncologist; only a minority preferred treatment by a mental health professional. These findings suggest that promoting education of oncologists to assess psychological symptoms and manage anxiety and depression as a routine part of an outpatient visit is beneficial

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with liver involvement.

BACKGROUND: We examined outcomes of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) combined with liver resection. METHODS: All patients undergoing CRS/HIPEC between 2007 and 2014 were retrospectively reviewed: patients who underwent synchronous liver resection (group 1) were compared with those who did not (group 2) in terms of perioperative and long-term results. RESULTS: Group 1 included 103 patients with colorectal cancer (CRC, n = 28), appendiceal cancer (n = 34), and other malignancies. Compared with group 2 (n = 166), group 1 had higher number of organs resected, increased intraoperative blood loss, and longer hospital stay (all P ≤ 0.004) but similar major morbidity (24.3% vs. 18.1%, P = 0.22) and perioperative mortality rates. Two patients from group 1 developed liver resection-related complications. A comparison between patients who underwent parenchymal liver resection (n = 42) and matched pairs from group 2 with similar extent of cytoreduction did not yield significant differences in morbidity/mortality. CRC patients from group 1 had poorer median overall survival (45.1 vs. 73.5 months from stage IV diagnosis, P = 0.009). CONCLUSIONS: Liver involvement denotes high peritoneal carcinomatosis burden, which often requires resection of multiple organs in order to achieve optimal cytoreduction. However, liver resection-related morbidity is low and overall morbidity/mortality rates are comparable to other extensive CRS/HIPEC procedures. J. Surg. Oncol. 2016;113:432-437. © 2016 Wiley Periodicals, Inc.

Prognostic Role of Immune Cells in Hepatitis B-associated Hepatocellular Carcinoma Following Surgical Resection Depends on Their Localization and Tumor Size.

This study aims to evaluate localized expression of CD4, interleukin (IL)-17, Foxp3, and CD8 in hepatitis B-associated hepatocellular carcinoma (HBV-HCC) and to explore their potential effects on outcome following surgical resection. This prospective study includes 66 HBV-HCC surgical resection patients enrolled from 2008 to 2013. CD4, IL-17, Foxp3, and CD8 mRNA in 4 regions of the resection specimens (center of the tumor, periphery of the tumor, non-neoplastic liver bordering tumor, non-neoplastic liver distant from tumor) was quantitated using real-time polymerase chain reaction. The tumoral regions had lower CD4 and CD8 expression as compared with paired non-neoplastic regions, whereas the expression of IL-17 and Foxp3 did not differ. High Foxp3 in all regions except non-neoplastic liver distant from tumor was associated with poor overall survival, whereas low CD8 expression in distant non-neoplastic liver may be associated with high HCC recurrence rate. Although the expression of almost all molecules did not differ between small (≤3 cm) and large HCC (>3 cm), high IL-17 in periphery of tumor, high CD8 in center of tumor, or low CD8 in distant non-neoplastic liver was associated with high HCC recurrence rate in patients with small HCC, but not in those with large HCC. The effect of immune cells on HCC progression therefore depends on the expression level, localization, and tumor size, and an imbalance toward regulatory T cells is associated with poor outcome.

Extreme cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Outcomes from a single tertiary center.

BACKGROUND: Multivisceral resection as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) may be required in order to achieve optimal debulking. This study aimed to assess perioperative and long-term outcomes of the most extensive CRS/HIPEC procedures. METHODS: All patients who underwent CRS/HIPEC at our institution between March 2007 and July 2014 were retrospectively reviewed. Patients undergoing extreme cytoreduction (n = 50), defined as a resection of ≥5 organs or ≥3 bowel anastomoses, were compared with patients who underwent less extensive procedures (n = 219). RESULTS: Complete cytoreduction (CC score ≤1) was achieved in 76% of the extreme CRS/HIPEC group, which included patients with colorectal cancer (CRC, n = 17), appendiceal adenocarcinoma (n = 20), gastric cancer (n = 6), and low-grade appendiceal neoplasm (n = 3). When compared with other patients undergoing CRS/HIPEC, the extreme CRS/HIPEC group had higher median PCI score, increased intraoperative blood loss, longer duration of surgery and longer hospital stay (all p values < 0.001). Major 30-day morbidity was significantly higher among the extreme CRS/HIPEC group (34% vs. 17.4%, p = 0.008) and there was also a trend towards higher 90-day mortality (12% vs. 5.1%, p = 0.07). Median disease free survival and overall survival in CRC patients undergoing extreme CRS/HIPEC was poorer (4.1 vs. 14.3 months, p = 0.01 and 10.1 vs. 43.8 months, p < 0.001, respectively). Extreme CRS/HIPEC was found to independently predict decreased overall survival in CRC patients. CONCLUSIONS: Extreme multivisceral resection as part of CRS/HIPEC is associated with higher major morbidity and inferior oncologic outcomes; therefore CRS/HIPEC provides the best outcomes in patients with fewer organs involved.

Myeloid-Derived Suppressor Cells as an Immune Parameter in Patients with Concurrent Sunitinib and Stereotactic Body Radiotherapy.

PURPOSE: The clinical effects of sunitinib on human myeloid-derived suppressor cell (MDSC) subsets and correlation of the T-cell-mediated immune responses and clinical outcomes in patients with oligometastases treated by stereotactic body radiotherapy (SBRT) have been evaluated. EXPERIMENTAL DESIGN: The numbers of granulocytic and monocytic MDSC subsets, effector T cells, and regulatory T cells in the peripheral blood were evaluated pre- and post-sunitinib treatment and concurrent with SBRT. Correlations between MDSC, Treg, and T-cell responses and clinical outcomes were analyzed. RESULTS: Patients with oligometastases of various cancer types had elevated granulocytic MDSC and certain subsets of monocytic MDSC population. Sunitinib treatment resulted in a significant reduction in monocytic MDSC, phosphorylated STAT3, and arginase levels in monocytic MDSC (CD33(+)CD14(+)CD16(+)), and an increase in T-cell proliferative activity in cancer patients. Interestingly, the effects of sunitinib on reducing the accumulation and immune-suppressive function of MDSC were significantly correlated with Treg reduction, in responders but not in nonresponding patients. SBRT synergized the therapeutic effects of sunitinib, especially as related to decreased numbers of monocytic MDSC, Treg, and B cells, and augmented Tbet expression in primary CD4 and CD8 T cells. These effects were not observed in patients receiving radiation therapy alone. Most interestingly, the responders, defined by sunitinib-mediated reduction in CD33(+)CD11b(+) myeloid cell populations, tend to exhibit improved progression-free survival and cause-specific survival. CONCLUSIONS: Sunitinib treatment increased the efficacy of SBRT in patients with oligometastases by reversing MDSC and Treg-mediated immune suppression and may enhance cancer immune therapy to prevent tumor recurrence post-SBRT.

Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma.

The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 µg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-µg NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4⁺ T-cell responses. CD8⁺ T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8⁺ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4⁺ T-cell responses in the majority of patients; the small proportion of CD8⁺ T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8⁺ T-cell responses.

Downstaging cancer in rural Africa.

Cancer is usually diagnosed late in rural Africa leading to incurability and abbreviated survival. Many curable cancers present on the body surface, often recognizable early by laymen as suspicious, justifying professional referral. Cancer diagnoses in two randomly chosen Tanzanian villages were compared after conventional dispensary self-referral vs. proactive visits in the home. Village navigators organized trips for professional consultation. In the control village 21% were self-referred, 20% of them were sent on as suspicious, 78% had cancer (8% in men) 0.9% of the village population. In the intervention village 99% were screened, 14% were referred for professional opinion, 93% had cancer (32% in men) 1.6% (p < 0.01 compared with control village). In the second and third years similar activity yielded 0.5% cancer annually in the control village for a 3 year total of 1.86% whereas interventional villagers had 1.4% and 0.6% cancer for a 3 year total of 3.56% (p < 0.001). Downstaging was recognized in the second and third years of intervention from 23 to 51 to 74% Stages I and II (p < 0.001) but in the control village Stages I and II changed from 11% to 22% to 37% (p = NS). The greatest downstaging occurred in breast and cervix cancers.

Comparative outcomes of elderly stage I lung cancer patients treated with segmentectomy via video-assisted thoracoscopic surgery versus open resection.

INTRODUCTION: Video-assisted thorcacic surgery (VATS) is considered an alternative to open lobectomy for the treatment of non-small-cell lung cancer (NSCLC). Limited data are available, however, regarding the equivalence of open versus VATS segmental resections, particularly among elderly patients. METHODS: From the Surveillance, Epidemiology, and End Results-Medicare database we identified 577 stage I NSCLC patients aged more than 65 years treated with VATS or open segmentectomy. We used propensity score methods to control for differences in the baseline characteristics of patients treated with VATS versus open segmentectomy. Outcomes included perioperative complications, need for intensive care unit, extended hospital stay, perioperative mortality, and survival. RESULTS: Overall, 27% of patients underwent VATS. VATS-treated patients had lower rates of postoperative complications (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.37-0.83), intensive care unit admissions (OR: 0.18, 95% CI: 0.12-0.28), and decreased length of stay (OR: 0.41, 95% CI: 0.21-0.81) after adjusting for propensity scores. Postoperative outcomes were not significantly different across groups after adjusting for surgeon characteristics. Overall (hazard ratio: 0.80, 95% CI: 0.60-1.06) and lung cancer-specific (hazard ratio: 0.71, 95% CI: 0.45-1.12) survival was similar across groups. CONCLUSIONS: VATS segmentectomy can be safely performed among elderly NSCLC patients and is associated with equivalent postoperative and oncologic outcomes.

Survival analysis of robotic versus traditional laparoscopic surgical staging for endometrial cancer.

OBJECTIVE: The purpose of this study was to compare the survival of women with endometrial cancer managed by robotic- and laparoscopic-assisted surgery. STUDY DESIGN: This was a retrospective study conducted at 2 academic centers. Primary outcomes were overall survival, disease-free survival (DFS), and disease recurrence. RESULTS: From 2003 through 2010, 415 women met the study criteria. A total of 183 women had robotic and 232 women had laparoscopic-assisted surgery. Both groups were comparable in age, body mass index, comorbid conditions, histology, surgical stage, tumor grade, total nodes retrieved, and adjuvant therapy. With a median follow-up of 38 months (range, 4-61 months) for the robotic and 58 months (range, 4-118 months) for the traditional laparoscopic group, there were no significant differences in survival (3-year survival 93.3% and 93.6%), DFS (3-year DFS 83.3% and 88.4%), and tumor recurrence (14.8% and 12.1%) for robotic and laparoscopic groups, respectively. Univariate and multivariate analysis showed that surgery is not an independent prognostic factor of survival. CONCLUSION: Robotic-assisted surgery yields equivalent oncologic outcomes when compared to traditional laparoscopic surgery for endometrial adenocarcinoma.

Assessing prognostic significance of preoperative alpha-fetoprotein in hepatitis B-associated hepatocellular carcinoma: normal is not the new normal.

BACKGROUND: Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear. METHODS: Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan­Meier analysis and multivariable Cox proportional hazards regression models. RESULTS: Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4-4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30-1.98), disease-free survival (HR = 1.26; 95 % CI 1.10-1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07-1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1-5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7-327,560.0 ng/mL) and Ishak stage 6 cirrhosis. CONCLUSIONS: Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC.