The impact of socioeconomic status on stage of cancer at diagnosis and survival

BACKGROUND:

Lower socioeconomic status (SES) is associated with worsened cancer survival. The authors evaluate the impact of SES on stage of cancer at diagnosis and survival in Ontario, Canada.

METHODS:

All incident cases of breast, colon, rectal, nonsmall cell lung, cervical, and laryngeal cancer diagnosed in Ontario during the years 2003‐2007 were identified by using the Ontario Cancer Registry. Stage information is captured routinely for patients seen at Ontario's 8 Regional Cancer Centers (RCCs). The Ontario population was divided into quintiles (Q1‐Q5) based on community median household income reported in the 2001 census; Q1 represents the poorest communities. Overall survival (OS) and cancer‐specific survival (CSS) were determined with Kaplan‐Meier methodology. A Cox model was used to evaluate the association between survival and SES, stage, and age.

RESULTS:

Stage at diagnosis was available for 38,431 of 44,802 (85%) of cases seen at RCCs. The authors observed only very small differences in stage distribution by SES. Across all cases in Ontario, the authors found substantial gradients in 5‐year OS and 3‐year CSS across Q1 and Q5 for breast (7% absolute difference in OS, P < .001; 4% CSS, P < .001), colon (8% OS, P < .001; 3% CSS, P = .002), rectal (9% OS, P < .001; 4% CSS, P = .096), nonsmall cell lung (3% OS, P = .002; 2% CSS, P = .317), cervical (16% OS, P < .001; 10% CSS, P = .118), and laryngeal cancers (1% OS, P = .045; 3% CSS, P = .011). Adjustments for stage and age slightly diminished the survival gradient only among patients with breast cancer.

CONCLUSIONS:

Despite universal healthcare, SES remains associated with survival among patients with cancer in Ontario, Canada. Disparities in outcome were not explained by differences in stage of cancer at time of diagnosis. Cancer 2010. © 2010 American Cancer Society.     

Disparities in survival among women with invasive cervical cancer

BACKGROUND:

In this study, the authors sought to understand the effects of patient race, ethnicity, and socioeconomic status (SES) on outcomes for cervical cancer.

METHOD:

The Florida Cancer Data System and the Agency for Health Care Administration data sets (1998‐2003) were merged and queried. Survival outcomes for patients with invasive cervical cancer were compared between different races, ethnicities, and community poverty levels.

RESULTS:

In total, 5367 patients with cervical cancers were identified. The overall median survival was 43 months. Significantly longer survival was observed for Caucasians (47.1 months vs 28.8 months for African Americans [AA]; P < .001), Hispanics (52.8 months vs 41.6 months for non‐Hispanics; P < .001), the insured (63 months vs 41.2 months for uninsured; P < .001), and patients from more affluent communities (53.3 months where <5% lived in poverty vs 36.9 months where >15% lived in poverty; P < .001). Surgery was associated with dramatically improved survival. AA women who were diagnosed with cervical cancer were significantly less likely to undergo surgical treatment with curative intent compared with Caucasian women (P < .001). However, on multivariate analysis, independent predictors of poorer outcomes were insurance status, tumor stage, tumor grade, and treatment. Neither race, nor ethnicity, nor SES was an independent predictor of poorer outcome.

CONCLUSIONS:

Race, ethnic, and SES disparities in cervical cancer survival were explained by late‐stage presentation and under‐treatment. Earlier diagnosis and greater access to surgery and other treatments would significantly improve the survival of women with cervical cancer. Cancer 2009. © 2008 American Cancer Society.     

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

BACKGROUND:

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.

METHODS:

Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re‐reviewed by genitourinary pathologists according to strict criteria.

RESULTS:

Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high‐grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) ‐positive. Over a mean follow‐up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5‐year recurrence‐free and cancer‐specific survival probabilities (±SD) were 69% ± 1% and 73% ± 1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P < .001), advancing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.8, P < .001), infiltrative growth pattern (HR: 1.5, P < .001), and LVI (HR: 1.2, P = .041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P = .001), high tumor grade (HR: 1.7, P = .001), increasing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.7, P < .001), sessile architecture (HR: 1.5, P = .002), and LVI (HR: 1.4, P = .02) were independently associated with cancer‐specific survival.

CONCLUSIONS:

Radical nephroureterectomy provided durable local control and cancer‐specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Cancer 2009. © 2009 American Cancer Society.     

Association of HPV35 with cervical carcinogenesis among women of African ancestry: Evidence of viral-host interaction with implications for disease intervention

HPV35 has been found in only ∼2% of invasive cervical cancers (ICC) worldwide but up to 10% in Sub-Saharan Africa, warranting further investigation and consideration of impact on preventive strategies. We studied HPV35 and ethnicity, in relation to the known steps in cervical carcinogenesis, using multiple large epidemiologic studies in the U.S. and internationally. Combining five U.S. studies, we measured HPV35 positivity and, in Northern California, observed HPV35 type-specific population prevalence and estimated 5-year risk of developing precancer when HPV35-positive. HPV35 genetic variation was examined for differences in carcinogenicity in 1053 HPV35+ cervical specimens from a U.S. cohort and an international collection. African-American women had more HPV35 (12.1% vs 5.1%, P < .001) and more HPV35-associated precancers (7.4% vs 2.1%, P < .001) compared to other ethnicities. Precancer risks after HPV35 infection did not vary by ethnicity (global P = .52). The HPV35 A2 sublineage showed an increased association with precancer/cancer in African-Americans (OR = 5.6 vs A1, 95% CI = 1.3-24.8) and A2 was more prevalent among ICC in Africa than other world regions (41.9% vs 10.4%, P < .01). Our analyses support a strong link between HPV35 and cervical carcinogenesis in women of African ancestry. Current HPV vaccines cover the majority of cervical precancer/cancer across all ethnic groups; additional analyses are required to determine whether the addition of HPV35 to the already highly effective nine-valent HPV vaccine would provide better protection for women in Africa or of African ancestry.     

The COVID - AGICT study: COVID–19 and advanced gastro-intestinal cancer surgical treatment. A multicentric Italian study on the SARS-CoV-2 pandemic impact on gastro-intestinal cancers surgical treatment during the 2020. Analysis of perioperative and short-term oncological outcomes

BackgroundThis Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic.MethodOur primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined.ResultsOverall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year ‘Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001).ConclusionsAlthough the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes.     

Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome

BACKGROUND:

Lymph node (LN) status after surgery for rectal cancer is affected by preoperative radiotherapy. The purpose of this study was to perform a population‐based evaluation of the impact of pathologic LN status (ypN) after neoadjuvant radiotherapy on survival.

METHODS:

Patients undergoing radical resection for rectal adenocarcinoma were identified from the Surveillance Epidemiology and End Results registry (1991‐2004). Patient characteristics, overall survival, and cancer‐specific survival (CSS) by ypN stage after surgery and use of preoperative or postoperative radiotherapy were compared.

RESULTS:

Of the 23,809 patients identified, 12,513 received preoperative (n = 5367) or postoperative (n = 7146) radiotherapy and resection. Preoperative patients were more likely to be younger (P < .001) and histopathologically free of detectable nodal metastasis (ypN0) than postoperative (51.8% vs 31.7%, P < .001). Median total numbers of LNs (6 vs 10) and positive LNs (2 vs 3) were lower among preoperative than postoperative (P < .001 for both). OS and CSS were similar among pN0 patients. However, on proportional hazards regression, ypN+ stage was associated with an increase in relative risk for death by 21% overall (hazard ratio [HR] = 1.21; 95% confidence interval 1.09‐1.35, P < .001) and 23% cancer‐specific (HR = 1.23; P = .001) for preoperative compared with postoperative.

CONCLUSIONS:

Pathologic LN status after neoadjuvant radiotherapy for rectal cancer is a biologic marker of prognosis. Patients who are ypN+ after preoperative are a subgroup of LN positive patients with adverse outcome. These high‐risk patients should be targeted for studies of novel multidisciplinary approaches, including expanded chemo‐ and biologic therapies. Cancer 2009. © 2009 American Cancer Society.     

Effect of Diphosphonates on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

Patients receiving androgen deprivation therapy are associated with increasing loss of bone mineral density (BMD) and higher risk of skeletal-related events. We reviewed and analyzed the influence of diphosphonates on BMD change. A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was BMD percentage change of lumbar spine, total hip, and femoral neck after 12 months. Standardized mean difference (SMD) was pooled with the random-effects model, and metaregression and subgroup analysis were performed to explore heterogeneity. Nine articles (n = 920) were included and finally analyzed after screening 118 articles. We found significant improvement in BMD percentage changes of the lumbar spine, total hip, and femoral neck at 1 year (respectively, SMD = 6.379, 95% confidence interval [CI] = 3.740-9.018, P < .001, I² = 98.8%, P < .001; SMD = 4.870, 95% CI, 2.256-7.485, P < .001, I² = 98.9%, P < .001; SMD = 3.634, 95% CI, 1.989-5.279, P < .001, I² = 97.3%, P < .001). In individual variable metaregression analysis, application zoledronic acid or not showed a statistically significant influence on BMD percentage change of total hip (P = .018). In subgroup analyses, both zoledronic acid and alendronate showed a significant improvement in BMD percentage changes. Diphosphonates significantly increased BMD percentage changes of the lumbar spine, total hip, and femoral neck in men receiving androgen deprivation therapy for prostate cancer. Patients with androgen deprivation therapy should be evaluated BMD loss, and timely therapy with diphosphonates may be an appropriate strategy to prevent osteoporosis.     

Are patients of low socioeconomic status receiving suboptimal management for pancreatic adenocarcinoma?

BACKGROUND:

The objective of this study was to define the effects of socioeconomic status (SES) and other demographic variables on outcomes for patients with pancreatic adenocarcinoma.

METHODS:

Florida cancer registry and inpatient hospital data were queried for pancreatic adenocarcinoma diagnosed from 1998 to 2002.

RESULTS:

In total, 16,104 patients were identified. Low SES (LSES) patients were younger at diagnosis (P < .001) but presented with similar disease stage and tumor grade. LSES patients were less likely to receive surgical extirpation (16.5% vs 19.8%; P < .001), chemotherapy (30.7% vs 36.4%; P < .001), or radiotherapy (14.3% vs 16.9%; P = .003). Among surgical patients, 30‐day mortality was significantly higher (5.1% vs 3.7%; P < .001) and overall median survival was significantly worse (5.0 months vs 6.2 months; P < .001) in the LSES cohorts. Although surgical patients who were treated at teaching facilities (TF) did significantly better; an increased 30‐day surgical mortality (2.2% vs 1.3%; P < .001) and decreased median survival (5 months for poverty level >15% vs 6.2 months for poverty level <5%; P < .001) also were observed for patients of LSES. In a multivariate analysis that corrected for patient comorbidities, significant independent predictors of a poorer prognosis included LSES (hazard ratio [HR], 1.09); treatment at a non‐TF (HR, 1.09); and failure to receive surgical extirpation (HR, 1.92), chemotherapy (HR 1.41), or radiation (HR 1.25).

CONCLUSIONS:

Patients of LSES were less likely to receive surgical extirpation, chemotherapy, or radiation and had significantly higher perioperative and long‐term mortality rates. A greater understanding of the barriers to providing optimal care and identifying means for improving successful delivery of therapies to the poor with pancreatic cancer are needed. Cancer 2010. © 2009 American Cancer Society.     

Understanding bladder cancer death

BACKGROUND:

To the authors' knowledge, the extent to which death from bladder cancer is attributable to tumor biology or physician practice patterns is unknown. For this reason, the relative importance of broadening indications for aggressive therapy has unclear implications.

METHODS:

Patients whose deaths were caused directly by bladder cancer were identified using institutional (n = 126 patients) and administrative (n = 6326 patients) data sources. By using implicit review (clinical data, 2001‐2005) and explicit algorithms (Surveillance, Epidemiology, and End Results [SEER]‐Medicare, 1992‐2002), the authors estimated the proportion of potentially avoidable deaths from bladder cancer.

RESULTS:

After an implicit review of clinical data, 40 of 126 deaths (31.7%) were classified as potentially avoidable. Compared with those patients who were deemed unsalvageable, these patients generally presented with nonmuscle‐invasive disease (80% vs 25.6%; P < .001), received multiple courses of intravesical therapy (32.5% vs 1.2%; P < .001), and had a more protracted course from diagnosis to aggressive treatment (median, 23 months vs 2 months; P < .001). An explicit review of claims data indicated that between 31.6% and 46.8% of the 6326 bladder cancer deaths identified in the SEER‐Medicare data potentially were avoidable, depending on the survivorship threshold chosen. Patients whose deaths potentially were avoidable more commonly presented with nonmuscle‐invasive disease (66.7% vs 24.7%; P < .0001) and lower grade disease (35.1% vs 15.1%; P < .0001).

CONCLUSIONS:

The greatest inroads into reducing death from bladder cancer likely hinge on earlier detection or improvement of systemic therapies. However, changing physician practice may translate into nontrivial reductions in bladder cancer mortality. Cancer 2009. © 2009 American Cancer Society.     

Possible role of Cdx2 in the serrated pathway of colorectal cancer characterized by BRAF mutation,high‐level CpG Island methylator phenotype and mismatch repair‐deficiency

Colorectal cancer is a heterogeneous disease at the histomorphological, clinical and molecular level. Approximately 20% of cases may progress through the “serrated” pathway characterized by BRAF mutation and high‐level CpG Island Methylator Phenotype (CIMP). A large subgroup are additionally microsatellite instable (MSI) and demonstrate significant loss of tumor suppressor Cdx2. The aim of this study is to determine the specificity of Cdx2 protein expression and CpG promoter hypermethylation for BRAF^V600E and high‐level CIMP in colorectal cancer. Cdx2, Mlh1, Msh2, Msh6, and Pms2 were analyzed by immunohistochemistry using a multi‐punch tissue microarray (TMA; n = 220 patients). KRAS and BRAF^V600E mutation analysis, CDX2 methylation and CIMP were investigated. Loss of Cdx2 was correlated with larger tumor size (P = 0.0154), right‐sided location (P = 0.0014), higher tumor grade (P < 0.0001), more advanced pT (P = 0.0234) and lymphatic invasion (P = 0.0351). Specificity was 100% for mismatch repair (MMR)‐deficiency (P < 0.0001), 92.2% (P < 0.0001) for BRAF^V600E and 91.8% for CIMP‐high. Combined analysis of BRAF^V600E/CIMP identified Cdx2 loss as sensitive (80%) and specific (91.5%) for mutation/high status. These results were validated on eight well‐established colorectal cancer cell lines. CDX2 methylation correlated with BRAF^V600E (P = 0.0184) and with Cdx2 protein loss (P = 0.0028). These results seem to indicate that Cdx2 may play a role in the serrated pathway to colorectal cancer as underlined by strong relationships with BRAF^V600E, CIMP‐high and MMR‐deficiency. Whether this protein can only be used as a “surrogate” marker, or is functionally involved in the progression of these tumors remains to be elucidated.     

China special issue on gastrointestinal tumors-Regulatory-immunoscore—A novel indicator to guide precision adjuvant chemotherapy in colorectal cancer

Novel biomarkers are essential to improve the treatment efficacy and overall survival of stage II and III colorectal cancer (CRC), allowing for personalized treatment decisions. Here, the densities of CD8⁺ and FOXP3⁺ T cells in the tumor and invasive margin were processed by immunohistochemistry and digital pathology to form a scoring system named regulatory-Immunoscore (RIS). Cox proportional hazards regression models were used to determine the risk factors associated with time to recurrence. Harrell's concordance index and the time-dependent area under the curve were used to assess model performance. A total of 1213 stage I-III DNA mismatch repair-proficient colorectal cancer (pMMR CRC) patients were randomly assigned to a training set (n = 642) and a validation set (n = 571). From the Cox multivariable analysis, the association of RIS with survival was independent of patient age, sex and anatomy-based tumor risk parameters (P < .0001). For stage II patients, chemotherapy was significantly associated with better recurrence time in patients with low (95% confidence interval [CI]: 0.11-0.54, P = .001) and intermediate (95% CI = 0.25-0.57, P < .001) RIS values. In stage III patients treated with adjuvant chemotherapy, a treatment duration of 6 or more months was significantly associated with better recurrence time in patients with intermediate RIS values (95% CI = 0.38-0.90, P = .016) when compared with duration under 6 months. Therefore, these findings suggest that RIS is reliable for predicting recurrence risk and treatment responsiveness for patients with stage I-III pMMR CRC.     

Intravenous therapy for chronic pulmonary aspergillosis: A systematic review and meta-analysis

Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening debilitating lung disease necessitating long-term oral antifungal treatment. However, development of antifungal-resistant isolates of Aspergillus and major toxicities requiring discontinuation of treatment limits their use. Intravenous (IV) antifungals are an option in this group of patients. We comprehensively evaluate the response rates to IV antifungals in the management of CPA. We searched Medline and Embase databases to select clinical studies providing information about IV amphotericin B or an echinocandin for the treatment of CPA from inception to May 2020. Reviews, single-case reports and case series reporting <10 patients were excluded. We evaluated 12 eligible studies. A total of 380 patients received amphotericin B (n = 143) or an echinocandin (n = 237) and were included in the meta-analysis. In a pooled analysis, overall response to IV antifungals was 61% ((95% confidence interval (CI): 52%-70%; I² = 73.3%; P < .001), to amphotericin B was 58% (95% CI: 36%-80%; I² = 86.6%; P < .001) and to echinocandins was 62% (95% CI: 53%-72%; I² = 63.6%; P < .001). Amphotericin B courses were usually doses at slightly <1 mg/Kg (deoxycholate) or 3 mg/Kg (liposomal) for 2-3 weeks. Micafungin doses varied from 12.5 to 300 mg (frequently, 150 mg) daily for at least 3 weeks, and sometimes much longer. Liposomal amphotericin B was well tolerated, but led to renal function loss in 25% of patients. Adverse events were observed in 5-35.3% of patients receiving echinocandins, none of which was considered major. Intravenous antifungals have a place in the management of CPA. A head-to-head comparison of amphotericin B and echinocandins is lacking, and future studies should look at evaluating short- and longer-term outcomes of these agents.     

Detection of hematogenous bone metastasis in cervical cancer

BACKGROUND:

In this large‐scale, retrospective study, the authors evaluated the diagnostic performances of computed tomography (CT), magnetic resonance (MR) imaging, and ¹⁸F‐fluorodeoxyglucose‐positron emission tomography (¹⁸F‐FDG–PET) in detecting hematogenous bone metastasis in patients with cervical cancer. The associated risk factors also were analyzed.

METHODS:

Patients with invasive cervical cancer who had both ¹⁸F‐FDG–PET studies and CT or MR imaging studies were selected. Patients who had either International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease or positive lymph node metastasis at the time of primary staging and patients who had suspected recurrent disease were included in the analyses. The diagnostic performances of PET was compared with the performance of CT and MR imaging by using the area under the receiver‐operating‐characteristic curve (AUC). Both univariate and multivariate analyses were applied to assess the risk factors for hematogenous bone metastasis at primary staging.

RESULTS:

PET was more sensitive than CT (P = .004) and was more specific than MR imaging (P = .04). The diagnostic performance of PET was significantly superior to the performance CT (AUC, 0.964 vs 0.662; P < .001) and MR (AUC, 0.966 vs 0.833; P = .033). Both FIGO stage and the extent of lymph node metastases were associated with hematogenous bone metastasis in univariate analysis. However, the extent of lymph node metastases was the only significant risk factor in multivariate analysis (P = .025).

CONCLUSIONS:

The current study demonstrated the superiority of ¹⁸F‐FDG–PET over CT and MR imaging for detecting hematogenous bone metastasis in patients with advanced cervical cancer. Hematogenous bone metastasis in cervical cancer was associated with the extent of lymph node metastases rather than with FIGO stage. Cancer 2009. © 2009 American Cancer Society.     

Results of the first phase 1 clinical trial of the HER‐2/neu peptide (GP2) vaccine in disease‐free breast cancer patients

BACKGROUND:

HER‐2/neu, overexpressed in breast cancer, is a source of immunogenic peptides that include GP2 and E75. Phase 2 testing of E75 as an adjuvant vaccine has suggested a clinical benefit. GP2, derived from the transmembrane portion of HER‐2/neu, has differing binding characteristics and may be more immunogenic than E75. Results of the first phase 1 trial of GP2 peptide vaccine are presented.

METHODS:

Disease‐free, lymph node‐negative, human leukocyte antigen (HLA)‐A2⁺ breast cancer patients were enrolled. This dose escalation trial included 4 groups to determine safety and optimal GP2 peptide/granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) dose. Toxicities were monitored. Immunologic response was assessed ex vivo via the HLA‐A2:immunoglobulin dimer assay to detect GP2‐specific CD8⁺ T cells (and E75‐specific CD8⁺ T cells to assess epitope spreading) and in vivo via delayed type hypersensitivity (DTH) reaction (medians/ranges).

RESULTS:

Eighteen patients were enrolled. All toxicities were grade ≤2. Eight (88.9%) of 9 patients in the first 3 dose groups required GM‐CSF dose reductions for local reactions ≥100 mm or grade ≥2 systemic toxicity. GM‐CSF dose was reduced to 125 μg for the final dose group. All patients responded immunologically ex vivo (GP2‐specific CD8⁺ T cells from prevaccination to maximum, 0.4% [0.0%‐2.0%] to 1.1% [0.4%‐3.6%], P < .001) and in vivo (GP2 pre‐ to postvaccination DTH, 0 mm [0.0‐19.5 mm] to 27.5 mm [0.0‐114.5 mm, P < .001). E75‐specific CD8⁺ T cells also increased in response to GP2 from prevaccination to maximum (0.8% [0.0%‐2.41%] to 1.6% [0.86%‐3.72%], P < .001).

CONCLUSIONS:

The GP2 peptide vaccine appears safe and well tolerated with minimal local/systemic toxicity. GP2 elicited HER‐2/neu–specific immune responses, including epitope spreading, in high‐risk, lymph node‐negative breast cancer patients. These findings support further investigation of the GP2 vaccine for the prevention of breast cancer recurrence. Cancer 2010. © 2010 American Cancer Society.     

The clinical application of 18F‐fluorodeoxyglucose positron emission tomography to predict survival in patients with operable esophageal cancer

BACKGROUND:

Metabolic tumor activity using ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) was believed to have a predictive value for patient outcome in malignancies. The objective of the current study was to assess the prognostic effectiveness of the highest standardized uptake value (SUV) in the primary or regional area (peak SUV) and the number of PET‐positive lymph nodes in esophageal cancer.

METHODS:

The authors retrospectively reviewed their experience with 184 consecutive esophageal cancer patients imaged preoperatively using FDG‐PET scanning.

RESULTS:

The median peak SUV was 4.5 (range, 1.4‐21.9). The survival curve was analyzed using the median peak SUV as the cutoff value. Comparison of each group and clinicopathologic characteristics revealed significant associations between peak SUV and each of the following factors: tumor status (P < .001), lymph node status (P < .001), metastatic status (P < .05), stage of disease (P < .001), number of PET‐positive lymph nodes (P < .001), and the number of histologically positive lymph nodes (P < .001). The 5‐year overall survival (OS) rate for patients having FDG uptake with a peak SUV ≥4.5 was 47% and that for patients with a peak SUV <4.5 was 76% (P < .0001). On multivariate survival analysis using the Cox proportional hazards model, peak SUV and the number of PET‐positive lymph nodes were found to be independent predictive factors for OS. The number of PET‐positive lymph nodes was a single prognostic factor predicting both disease‐free survival and OS.

CONCLUSIONS:

Pretreatment PET cannot only potentially diagnose the extent of disease, but also may be predictive of patient survival after esophageal cancer resection. Cancer 2009. © 2009 American Cancer Society.     

Long-term prognostic impact of cardiovascular comorbidities in patients with prostate cancer receiving androgen deprivation therapy: A population-based competing risk analysis

Our study investigated how adverse cardiovascular outcomes are impacted by cardiovascular comorbidities in patients with prostate cancer treated by androgen deprivation therapy (ADT). Using prospective, population-based data, all Hong Kong patients with prostate cancer who received ADT during 1 January 1993 to 3 March 2021 were identified and followed up for the endpoint of cardiovascular hospitalization/mortality until 31 September 2021, whichever earlier. Multivariable competing risk regression was used to compare the endpoint's cumulative incidence between different combinations of major cardiovascular comorbidities (heart failure [HF], myocardial infarction [MI], stroke and/or arrhythmia), with noncardiovascular death as competing event. Altogether, 13 537 patients were included (median age 75.9 [interquartile range 70.0-81.5] years old; median follow-up 3.3 [1.5-6.7] years). Compared to those with none of prior HF/MI/stroke/arrhythmia, the incidence of the endpoint was not different in those with only stroke (subhazard ratio [SHR] 1.06 [95% confidence interval (CI): 0.92-1.23], P = .391), but was higher in those with only HF (SHR 1.67 [1.37-2.02], P < .001), arrhythmia (SHR 1.63 [1.35-1.98], P < .001) or MI (SHR 1.43 [1.14-1.79], P = .002). Those with ≥2 of HF/MI/stroke/arrhythmia had the highest incidence of the endpoint (SHR 1.94 [1.62-2.33], P < .001), among whom different major cardiovascular comorbidities had similar prognostic impacts, with the number of comorbidities present being significantly prognostic instead. In conclusion, in patients with prostate cancer receiving ADT, the sole presence of HF, MI or arrhythmia, but not stroke, may be associated with elevated cardiovascular risks. In those with ≥2 of HF/MI/stroke/arrhythmia, the number of major cardiovascular comorbidities may be prognostically more important than the type of comorbidities.     

Carcinoma of the upper urinary tract

BACKGROUND:

Carcinomas of the upper urinary tract are uncommon tumors that usually occurred in elderly patients. Competing causes of mortality should be considered when treating these patients.

METHODS:

All patients with upper urinary tract tumors who were treated surgically at Centre Hospitalier Universitaire de Québec and affiliated hospitals from 1978 to 2001 were retrospectively reviewed. Clinical and pathologic variables were assessed from both the preoperative and postoperative periods of management, and clinical outcomes were tracked. Competing risks regression, Cox proportional hazards modeling, and multiple imputation were used to assess predictors of cancer‐related and competing risks?related mortality in both preoperative and postoperative settings.

RESULTS:

Competing risks were responsible for 46% of deaths in this cohort of 168 patients. Preoperatively, the most important predictor of cancer‐related mortality was a clinically invasive tumor (hazards ratio [HR], 3.97; P < .001), whereas increasing age (HR, 1.07; P < .001) was found to be the most important predictor of competing mortality. Postoperatively, tumor grade was the most important predictor of cancer‐related mortality (HR, 3.92; P < .001) whereas constitutional symptoms (HR, 1.91; P = .015) and increasing age (HR, 1.06; P < .001) were found to be predictive of competing mortality.

CONCLUSIONS:

In the current study, stage and grade were found to be the 2 most important independent predictors of survival in patients with tumors of the upper urinary tract and were highly correlated. Pain or weight loss was found to be a novel predictor of survival in this cancer. Although a survival disadvantage was not noted for women, nephron‐sparing surgery, ureteral tumors, or older patients with respect to cancer, competing causes of mortality were found to be responsible for greater than one‐third of observed deaths and age was the best predictor of this occurrence. Cancer 2009. © 2009 American Cancer Society.     

HPV-induced host epigenetic reprogramming is lost upon progression to high-grade cervical intraepithelial neoplasia

The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic human papilloma virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV-induced host epigenome-wide changes prior to development of cytological abnormalities. Using cervical sample methylation array data from disease-free women with or without an oncogenic HPV infection, we develop the WID (Women's cancer risk identification)-HPV, a signature reflective of changes in the healthy host epigenome related to high-risk HPV strains (AUC = 0.78, 95% CI: 0.72-0.85, in nondiseased women). Looking at HPV-associated changes across disease development, HPV-infected women with minor cytological alterations (cervical intraepithelial neoplasia grade 1/2, CIN1/2), but surprisingly not those with precancerous changes or invasive cervical cancer (CIN3+), show an increased WID-HPV index, indicating the WID-HPV may reflect a successful viral clearance response absent in progression to cancer. Further investigation revealed the WID-HPV is positively associated with apoptosis (ρ = 0.48; P < .001) and negatively associated with epigenetic replicative age (ρ = −0.43; P < .001). Taken together, our data suggest the WID-HPV captures a clearance response associated with apoptosis of HPV-infected cells. This response may be dampened or lost with increased underlying replicative age of infected cells, resulting in progression to cancer.     

Prognostic Model to Identify Patients With Myelofibrosis at the Highest Risk of Transformation to Acute Myeloid Leukemia

BackgroundSome patients with myelofibrosis (MF) progress to acute myeloid leukemia (AML). Current prognostic tools were not devised to assess risk of AML transformation.MethodsMultivariate analysis in 649 patients followed for a median of 19 months (range, 1-180 months).ResultsWe identified age > 60 (P = .004; hazard ratio [HR], 1.63), platelets <100 × 10⁹/L (P < .001; HR, 1.62), bone marrow blast > 10% (P = .002; HR, 2.18), high-risk karyotype (P < .001; HR, 2.44), transfusion dependency (P < .001; HR, 2.64), performance status > 1 (P = .003; HR, 1.47), lactate dehydrogenase > 2000 U/L (P < .001; HR, 1.62), previous hydroxyurea (P < .001; HR, 1.69), and male sex (P = .005; HR, 1.41) as independent poor prognostic factors for survival. Using the same baseline variables we identified bone marrow blasts >10% and worst karyotype as independent risk factors for AML transformation. Patients with 1 or both of these risk factors (n = 80; 12%) had a median survival of 10 months and a 1-year AML transformation rate of 13% (2% if none of those factors, P = .001).ConclusionWe have identified risk factors that predict high risk of transformation from MF to AML.