This paper briefly illustrates the basis, rules of application, and present outcome of the current World Health Organization (WHO) classification for neuroendocrine neoplasms. Established in 2010 upon the proposal from the European Neuroendocrine Tumor Society (ENETS), the WHO 2010 fostered some definitional changes (most notably the use of neuroendocrine tumor (NET) instead of carcinoid) and indicated the tools of grading and staging. Specific rules for its application were also defined. The data generated from the use of WHO 2010 classification substantially endorsed its rules and prognostic efficacy. In addition, the application demonstrated some issues, among which are the possible re-definition of the cutoff for grading G1 vs G2, as well as the possible identification of cases with somewhat different clinical behavior within the G3 neuroendocrine cancer class. Overall, since the recent introduction of WHO 2010 grading and staging, it appears wise to keep the current descriptors to avoid unnecessary confusion and to generate comparable data. Homogenous data on large series are ultimately needed to solve such issues.
To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade.
All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged =70 years; had serum PSA concentration of
Active surveillance has evolved to become a standard of care for favorable-risk prostate cancer. This article is a summary of the rationale, method, and results of active surveillance beginning in 1995 with the first prospective trial of this approach.
This was a prospective, single arm cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a prostate specific antigen (PSA) doubling time of less than 3 years, Gleason score progression (to 4?+?3 or greater), or unequivocal clinical progression. Since November 1995, 450 patients have been managed with active surveillance. Median follow-up is 6.8 years (range 1-16 years). Overall survival is 78.6%. Ten-year prostate cancer actuarial survival is 97.2%. Five of 450 patients (1.1%) have died of prostate cancer. Thirty percent of patients have been reclassified as higher risk and offered definitive therapy. The commonest indication for treatment was a PSA doubling time less than 3 years (48%) or Gleason upgrading (26%). Of 117 patients treated radically, the PSA failure rate was 50%. This represents 13% of the total cohort. Most PSA failures occurred early; at 2 years, 44% of the treated patients had PSA failure. The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years.
We observed a very low rate of prostate cancer mortality in an intermediate time frame. Among the one-third of patients who were reclassified as higher risk and retreated, PSA failure was relatively common. However, other cause mortality accounted for almost all of the deaths. Further studies are warranted to improve the identification of patients who harbor more aggressive disease in spite of favorable clinical parameters at diagnosis.
Active surveillance has evolved to become a standard of care for favorable-risk prostate cancer. This is a summary of the rationale, method, and results of active surveillance beginning in 1995 with the first prospective trial of this approach. This was a prospective, single-arm cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression (to 4+3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data. Since November 1995, 450 patients have been managed with active surveillance. The cohort included men under 70 with favorable-risk disease and men of age more than 70 with favorable- or intermediate-risk cancer (Gleason score 3+4 or PSA 10-15). Median follow-up is 6.8 years (range 1-16 years). Overall survival is 78.6%. Ten-year prostate cancer actuarial survival is 97.2%. Five of 450 patients (1.1%) have died of prostate cancer. Thirty percent of patients have been reclassified as higher-risk patients and offered definitive therapy. The commonest indication for treatment was a PSA doubling time less than 3 years (48%) or Gleason upgrading (26%). Of 117 patients treated radically, the PSA failure rate was 50%. This represents 13% of the total cohort. Most PSA failures occurred early; at 2 years, 44% of the treated patients had PSA failure. The hazard ratio for non-prostate cancer mortality to prostate cancer mortality was 18.6 at 10 years. In conclusion, we observed a very low rate of prostate cancer mortality in an intermediate time frame. Among the one-third of patients who were reclassified as higher risk and retreated, PSA failure was relatively common. However, other-cause mortality accounted for almost all of the deaths. Further studies are warranted to improve the identification of patients who harbor more aggressive disease in spite of favorable clinical parameters at diagnosis [reproduced from Klotz (1) with permission from Wolters Kluwer Health].
Evidence suggests that pre- and/or postoperative treatment benefits patients with stage II/III rectal cancer. This study aimed to quantify treatment patterns and adherence to treatment guidelines, and to identify barriers to having a consultation with an oncologist and barriers to receiving treatment in stage II/III rectal cancer, in a publicly funded medical care system.
Patients with surgically treated stage II/III rectal adenocarcinoma, diagnosed from 2002 to 2005 in Alberta, a Canadian province with a population of 3 million, were included. Demographic and treatment information from the Alberta Cancer Registry were linked to data from electronic medical records, hospital discharge data and the 2001 Canadian Census. The study outcomes were 'not having an oncologist consultation' and 'not receiving guideline-based treatment'. The relative risks of the two outcomes in association with patient characteristics were estimated using multivariable log-binomial regression.
Of a total of 910 surgically treated stage II/III rectal adenocarcinoma patients, 748 (82%) had a consultation with an oncologist and 414 (45.5%) received treatment. Pre-/post-surgical treatment modalities and timing varied; 96 (10.5%) received neoadjuvant treatment only, 389 (42.7%) received adjuvant treatment only, 119 (13.1%) received both, and 306 (33.6%) had surgery alone. Factors related to not having a consultation with an oncologist included older age, co-morbidities, cancer stage II and region of residence. Older age was the most significantly associated factor with not receiving treatment (relative risk=2.23; 95% confidence interval: 1.89, 2.64).
Disparities exist in the receipt of treatment in stage II/III rectal cancer. Factors such as age, region of residence and stage should not be barriers to consulting an oncologist to discuss or receive treatment. The reasons for these disparities need to be identified and addressed.
Capecitabine is an active agent in the treatment of breast cancer. It is not known whether integration of capecitabine into an adjuvant regimen that contains a taxane, an anthracycline, and cyclophosphamide improves outcome in early breast cancer.
Women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive either three cycles of docetaxel and capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX; n = 753) or three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF; n = 747). The primary end point was recurrence-free survival (RFS).
During a median follow-up time of 59 months, 214 RFS events occurred (local or distant recurrences or deaths; TX/CEX, n = 96; T/CEF, n = 118). RFS was not significantly different between the groups (hazard ratio [HR], 0.79; 95% CI, 0.60 to 1.04; P = .087; 5-year RFS, 86.6% for TX/CEX v 84.1% for T/CEF). Fifty-six patients assigned to TX/CEX died during the follow-up compared with 75 of patients assigned to T/CEF (HR, 0.73; 95% CI, 0.52 to 1.04; P = .080). In exploratory analyses, TX/CEX improved breast cancer-specific survival (HR, 0.64; 95% CI, 0.44 to 0.95; P = .027) and RFS in women with triple-negative disease and in women who had more than three metastatic axillary lymph nodes at the time of diagnosis. We detected little severe late toxicity.
Integration of capecitabine into a regimen that contains docetaxel, epirubicin, and cyclophosphamide did not improve RFS significantly compared with a similar regimen without capecitabine.
Comment In: J Clin Oncol. 2012 Jan 1;30(1):1-222105825
Intermittent dosing may reduce the adverse events (AEs) of androgen-deprivation therapy (ADT).
To compare intermittent androgen deprivation (IAD) and continuous androgen deprivation (CAD) with regard to health-related quality of life (QoL).
A total of 852 men with advanced prostate cancer (PCa) were enrolled to receive goserelin acetate 3.6 mg every 28 d for 24 wk. A total of 554 patients whose prostate-specific antigen (PSA) decreased to 20 ng/ml or above baseline.
QoL was monitored with a validated Cleary 30-item questionnaire and analysed by the Mann-Whitney U test, 0.5 standard deviation rule, and repeated measures analysis of variance. AEs and adverse drug reactions (ADRs) were analysed by the chi-square test.
Median follow-up was 65 mo. Significant differences in QoL emerged in activity limitation, physical capacity, and sexual functioning, favouring IAD. No significant differences emerged in the prevalence of AEs: 87 patients in the IAD arm (31.8%) and 95 in the CAD arm (33.9%) had cardiovascular (CV) AEs (p=0.59), with 25 (9.1%) and 29 (10.4%) withdrawn (p=0.62), and 21 (7.7%) and 24 (8.6%) dying because of a CV event (p=0.70), respectively; bone fractures occurred in 19 (6.9%) and 15 (5.4%) patients (p=0.44), respectively. Hot flushes or night sweats were the most common ADRs (47.1% vs 50.4%; p=0.44). Erectile dysfunction (15.7% vs 7.9%; p=0.042) and depressed mood (2.2 vs 0%; p=0.032) were more common in the IAD arm.
IAD showed benefits in the treatment of advanced PCa with respect to QoL. The prevalence of AEs was not significantly lower with IAD.
We analyzed the association of polymorphic variants of rs917997 (G/A) locus in IL18RAP gene and rs187238 (G/C) locus in IL18 gene with the risk of malignant non-Hodgkin's lymphomas in Novosibirsk population. Allele and genotype frequencies of the above loci were determined in patients (243 persons) and control group (371 persons) and compared using ?(2) test. None of the analyzed loci showed statistically significant association with the risk of malignant non-Hodgkin's lymphomas.
The increase in clinical trials with androgen receptor (AR)-targeting drugs emphasizes the need of clarifying the role of AR expression in different breast cancer subtypes. AR confers good prognosis in estrogen receptor positive (ER+) breast cancer, but its role in ER-negative (ER-) breast cancer is unclear. The aim of this study was to elaborate on previous findings of a differential prognostic role for AR depending on ER status, using breast cancer mortality (BCM) as endpoint, in a population-based cohort from the Malmö Diet and Cancer Study.
Immunohistochemical AR expression was assessed in 910 women with invasive breast cancer diagnosed 1991-2010, supplemented with clinicopathological information, vital status, and cause of death, with the last follow-up in December 2014 (median 10 years). Survival analyses according to AR status and AR/ER combinations were performed.
AR expression was available for 671 tumors. AR+ (n = 573, 85%) was associated with favorable established tumor markers and lower BCM in univariable analysis, especially during the first 5 years following diagnosis [HR 0.4; 95% confidence intervals (CI) 0.2-0.7]. Multivariable analysis for short-term follow-up indicated higher BCM among patients with AR+ER- tumors (HR 3.5; 95% CI 1.4-9.1) than other AR and ER combinations.
AR expression added prognostic information to ER expression with respect to short-term prognosis. The worst prognosis was seen for patients with AR+/ER- tumors in short-term follow-up, supporting the pre-specified hypothesis. However, larger cohorts are needed for further characterization of the role of AR expression in ER- breast cancer.
Cites: J Natl Cancer Inst. 2014 Jan;106(1):djt319 PMID 24273215
Cites: Cancer Res. 2009 Aug 1;69(15):6131-40 PMID 19638585
After surgical resection for oral cavity squamous cell carcinoma, adjuvant radiotherapy may be recommended for patients at higher risk for locoregional recurrence, but it can be difficult to predict whether a particular patient will benefit.
To construct a model to predict which patients with oral cavity squamous cell carcinoma would benefit from adjuvant radiotherapy.
We constructed several types of survival models using a set of 979 patients with oral cavity squamous cell carcinoma. Covariates were age, sex, tobacco use, stage, grade, margins, and subsite. The best performing model was externally validated on a set of 431 patients.
The model was based on a set of 979 patients with oral cavity squamous cell carcinoma, including 563 from Memorial Sloan Kettering Cancer Center, New York, New York, and 416 from the Hospital AC Camargo, São Paulo, Brazil. The validation set consisted of 431 patients from Princess Margaret Hospital, Toronto, Ontario, Canada.
The primary outcome measure of interest was locoregional recurrence-free survival.
The lognormal model showed the best performance per the Akaike information criterion. An online nomogram was built from this model that estimates locoregional failure-free survival with and without postoperative radiotherapy.
A web-based nomogram can be used as a decision aid for adjuvant treatment decisions for patients with oral cavity squamous cell carcinoma.