Low-risk Stage Research Articles

Quality of timely adjuvant chemotherapy for veterans with colorectal cancer.

78 Background: National Comprehensive Cancer Network (NCCN) recommends adjuvant chemotherapy for patients with high risk stage II or stage III colorectal cancer (CRC). Treatment within 8 weeks of surgery improves disease free survival and decreases recurrence. National Veterans Health Administration (VHA) CRC data demonstrated adherence to this standard; however, there was regional variation. We sought to describe time to treatment at a Southeast Regional VHA facility to determine local targets for quality improvement initiatives. Methods: We retrospectively reviewed 705 electronic medical records of patients who underwent colorectal surgery from January 1, 2000 to December 31, 2015 at VHA Tennessee Valley Healthcare System. Two trained clinician abstractors reviewed standard elements (k = 0.79 – 0.92). The population included patients with pathological stage high risk II or III CRC and excluded those with metastatic disease or documented NCCN defined exclusion from chemotherapy. We analyzed 2 populations; chemotherapy received and a sensitivity analysis population of patients who were eligible for, but did not receive, chemotherapy (no documentation of NCCN ineligibility or declined). The primary outcome was chemotherapy within 8 weeks of surgery, evaluated during three time periods due to changes in NCCN guidelines. Results: Of 705 colorectal surgeries, we excluded 262 for non-cancers, 220 for stage I or low-risk stage II cancers, and 46 for NCCN defined exclusion, yielding 177 cases: 120 colon and 57 rectal cancers. Patients were 98% male, 85% white, and median age 64 years [Interquartile Range 60, 70]. Among those receiving chemotherapy (123/177 [69.5%]), median time to treatment was 50.5 days [40,64]; with 63% receiving chemotherapy within 8 weeks. Results varied over time. Between 2000-2004 75% received within 8 weeks; 2005-2009, 62%; 2010-2015, 41%. Including all eligible patients, the proportion receiving timely treatment declined; overall 44%; 2000-2004, 57%; 2005-2009, 45%; 2010-2015, 25%. Conclusions: Improving care processes for patients with CRC can improve timely treatment. Exploring barriers such as prolonged hospitalization, wound healing, and port placement may reveal areas for quality improvement.

Relatively low risk and nonaggressive stage of colorectal cancer in individuals with negative baseline fecal immunochemical test results: A cohort study

AbstractFecal immunochemical testing (FIT) is used as a screening tool because of its adequate sensitivity to detect colorectal cancer (CRC). Whether individuals with negative baseline FIT results have a low risk of CRC over a long period of follow‐up remains unclear. This retrospective cohort study investigated the characteristics of CRC in individuals with normal baseline FIT results. We retrospectively evaluated individuals who participated in the Taiwanese biennial FIT‐based CRC screening program at a single hospital between March 2010 and December 2017. Patients who had positive FIT results (≥30 μg Hb/g feces) and then underwent confirmatory colonoscopy were enrolled for further analysis. Patients were divided into two cohorts: target group (consisting of patients with negative FIT results in the baseline round, followed by positive FIT results and confirmatory colonoscopy in any one of the subsequent rounds) and reference group (consisting of patients with positive FIT results in the baseline round and confirmatory colonoscopy). The detection rate and characteristics of CRC were compared between two groups. A P value of <.05 was considered statistically significant. A total of 51 789 individuals underwent 80 195 tests in four rounds of biennial FIT based CRC screening. The positivity rate of FIT was 8.2% (n = 6591). The colonoscopy compliance rate was 70.3% (n = 4635). From 4635 individuals, 1650 and 2985 were included in the target and reference groups, respectively. The CRC detection rate in the target and reference groups was 2.3% (38/1650) and 5.0% (149/2985), respectively (odds ratio = 0.45; 95% confidence interval = 0.31‐0.64). The CRC detection rate in the target group increased with screening intervals (P for trend = .001). After excluding patients with unknown stage, 35 patients in the target group and 130 patients in the reference group were included for subsequent analysis. Lesions were located mainly in the distal colon in both groups (82.9% [29/35] vs. 82.3% [107/130]; P = 1). The distribution of the CRC stage according to the seventh edition of the American Joint Committee on Cancer staging system in the target vs reference group was as follows: Stage 0: 48.6% vs 20.0%; Stage I: 11.4% vs 30.0%; Stage II: 20.0% vs 18.5%; Stage III: 17.1% vs 22.3%; and Stage IV: 2.9% vs 9.2%; (P = .008). CRC detection rate declined considerably if the baseline FIT result was negative. CRC detected in patients with negative baseline FIT results showed a high proportion of nonaggressive stage. Approximately 80% of CRCs were identified in the left‐sided colon, suggesting the limited ability of repetitive FIT to detect proximal CRC. These results support the benefits and necessity of consecutive FIT screening even when the baseline FIT result is negative.

Comparative efficacy and tolerability of adjuvant systemic treatments against resectable colon cancer: a network meta-analysis.

Background:Currently, 6-month oxaliplatin-based chemotherapy has been recommended as the preferred adjuvant treatment against high-risk stage 2 and stage 3 colon cancer patients.Methods:Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology and European Society for Medical Oncology meeting libraries from inception to November 2019. Regarding survival and tolerability, randomized controlled trials comparing different adjuvant systemic regimens against high-risk stage 2 and stage 3 colon cancer were eligible. Disease-free survival was primary endpoint. Network calculation was based on a random-effects model, and relative ranking of each node was numerically indicated by p score.Results:A total of 30 trials were included, corresponding to 54,109 patients. Regarding disease-free survival, none of the analyzed regimens displayed significant superiority against common comparator 6-month capecitabine plus oxaliplatin (XELOX), while 12-month [network hazard ratio (HR) 0.81 (0.60–1.10); 0.79 (0.57–1.10)] and 3-month XELOX [0.95 (0.86–1.04); 0.93 (0.83–1.05)] were top-ranking regimens showing non-inferiority among overall and stage 3 patients. Moreover, by pairwise meta-analysis, 3-month XELOX demonstrated significant superiority against 6-month XELOX among low-risk stage 3 patients [pairwise HR 0.78 (0.63–0.97)]. Concerning adverse events, 3-month oxaliplatin-based chemotherapy was significantly better than the 6-month counterpart with respect to peripheral sensory neuropathy, thrombocytopenia and fatigue. The 12-month capecitabine monotherapy failed to display non-inferiority among other major adverse events.Conclusions:The 3-month XELOX treatment could be an alternative option of the 6-month regimen among low-risk stage 3 patients. Among high-risk stage 3 patients, 6-month oxaliplatin-based regimens still seem more competitive. In addition, clinical application of 12-month capecitabine monotherapy should be cautious, despite its top rankings, especially among non-Asian countries.

Survival and recurrence in stage II endometrial cancers in relation to uterine risk stratification after introduction of lymph node resection and omission of postoperative radiotherapy: a Danish Gynecological Cancer Group Study.

ObjectiveTo evaluate survival and recurrence in stage II endometrial cancer in relation to uterine risk stratification. Outcome for stage II was compared before and after the introduction of lymph node (LN) resection and omission of all postoperative radiotherapy.MethodsThe cohort consisted of 4,380 endometrial carcinoma patients radically operated (no visual tumor, all distant metastasis removed) (2005–2012) including 461 stage II. Adjusted Cox regression was used to compare survival and actuarial recurrence rates.ResultsUterine risk factors (low-, intermediate-, and high-) were the strongest predictors of survival and recurrence in stage II. Stage II low-risk having a prognosis comparable to low-risk stage I (grade 1–2, <50% myometrial invasion), whereas cervical invasion significantly increased the risk of recurrence and decreased cancer-specific survival in intermediate- and high-risk compared to the corresponding stage I risk groups. In 355 cases of 708 with cervical stromal invasion, LN-resection showed 27.9% with LN metastasis and upstaged 18.1% from stage II to IIIC resulting in longer survival and lower recurrence in LN-resected compared to non-LN resected stage II. Radical as compared to simple hysterectomy did not alter survival. Treatment with external beam radiotherapy decreased local recurrence without affecting survival.ConclusionUterine risk groups are the strongest predictors for survival and recurrence in stage II patients and should be considered when advising adjuvant therapy. LN-resected stage II had increased survival and decreased recurrence. Omitting radiotherapy increase vaginal recurrence without affecting survival.

Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates between stages. Importantly, a direct comparison of low-risk and high-risk stages revealed epigenetic traits characteristic of high-risk tumours. Finally, a prognostic prediction model in cSCC patients identified a methylation signature able to predict the overall survival of patients. Thus, the analysis of DNA-methylation in cSCC revealed changes during the evolution of the disease through the different stages that can be of great value not only in the diagnosis but also in the prognosis of the disease.

Survival outcomes of low-risk and intermediate-risk stage IB1 cervical cancer patients

Abstract Background Survival for patients with early stage cervical cancer without any high-risk factors treated with radical hysterectomy is excellent. However, there are few data on the survival outcomes for low-risk and intermediate-risk early stage cervical cancer patients. Objective To determine survival outcomes and prognostic factors of low-risk and intermediate-risk stage IB1 cervical cancer patients. Methods Stage IB1 cervical cancer patients with radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. Patients with positive pelvic nodes, parametrial involvement, and positive margin who are classified as high-risk patients were excluded. Patients with squamous cell carcinoma or grade 1–2 adenocarcinoma, tumor size less than 2 cm, no lymphovascular space invasion (LVSI), and depth of stromal invasion (DSI) less than 10 mm were defined as low-risk patients. Survival was evaluated using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was performed using Cox proportional-hazards regression. Results There were 82 (42.3%) low-risk patients and 112 (57.7%) intermediate-risk patients. More patients in intermediate risk received adjuvant treatment (3.6% and 14.3%, P = 0.07). Three (3.6%) low-risk patients and 18 (16.1%) intermediate-risk patients had recurrent disease (P = 0.004). At median follow-up of 86 months, 1.2% of low-risk patients and 8.9% of intermediate-risk had cancer-related deaths (P = 0.02). Low-risk patients had significantly better 5-year disease-free survival (98.2% vs 91.1%, P = 0.01) and estimated 5-year overall survival (98.5% vs 91.1%, P = 0.01). DSI more than 10 mm and presence of LVSI were significantly associated with recurrence. However, LVSI was an independent prognostic factor. Conclusion Stage IB1 cervical cancer patients had excellent survival. Low-risk patients had significantly better survival. Presence of LVSI was an independent prognostic factor.

Making sense of adjuvant chemotherapy in colorectal cancer.

Surgical resection is the only curative treatment for locoregional colon cancer. The goal of adjuvant chemotherapy is to eradicate micro-metastatic disease and improve survival. This has been most clearly demonstrated in stage III (node-positive) disease, whereas benefit of adjuvant chemotherapy in stage II disease remains controversial. In stage III colon cancer, 6 months of adjuvant chemotherapy with oxaliplatin-based chemotherapy have been accepted as the standard for the last 15 years. The recent IDEA collaboration has challenged this in 2018; while overall was a negative non-inferiority study, pre-planned subset analyses do support that for patients with low-risk stage III disease, 3 months of XELOX (capecitabine and oxaliplatin combination) is non-inferior to 6 months. In stage II colon cancer, where the potential benefit of adjuvant chemotherapy is small, the emergence of biomarkers has helped in decision-making. Tumors with deficient mismatch repair protein (dMMR) do not benefit from 5-fluorouracil-based chemotherapy. For patients with high clinicopathological risk stage II disease with proficient mismatch repair proteins and good performance status, six months of adjuvant chemotherapy is still recommended. In the management of rectal cancers, where the risk of local recurrence is higher, chemoradiation (CRT) is often included as neoadjuvant or adjuvant therapy in the management of stage II and III rectal cancer. The benefit of adjuvant chemotherapy in rectal cancer has been extrapolated from adjuvant colon cancer studies with updated results from adjuvant rectal cancer studies demonstrating similar benefits. This review summarizes the current landscape of adjuvant therapy for patients with resected stage II and III colorectal cancer.

555P - Impact of the IDEA study on clinical practice for stage III colon cancer patients: A French GERCOR - FFCD - GI UNICANCER national survey

BackgroundThe IDEA study showed that the type and duration of adjuvant chemotherapy in stage III colon cancer (CC) could be adjusted according to level of risk (Grothey et al., New Engl J Med 2018). One year after the publication of IDEA study, we performed an audit of real-life practices in France. MethodsWe conducted an online anonymized nationwide survey from January 30, 2019 to March 31, 2019. An invitation email followed by reminders every 2 weeks was sent to clinicians using the oncology cooperative groups GERCOR, FFCD and GI UNICANCER mailing lists. All of the answers were declarative, individual, and anonymized. Proportions were compared using chi-squared test. ResultsA total of 213 physicians answered the survey: 31% worked in an academic hospital, 27% in a general hospital, 26% in a comprehensive cancer center and 16% in a private clinic. Main responders were gastroenterologists (51%) or medical oncologists (39%). 47% of physicians took care of more than 12 stage III CC patients per year. For low risk stage III CC (T1-T3 and N1), 81% preferred a 3-month duration of treatment, and 74% used capecitabine plus oxaliplatine (CAPOX) as the standard regimen. 66% of CAPOX for 3 months were realized without central venous access device, which was necessary during treatment in less than 25% of cases according to 68% of the responders. Physicians choosing 6-month duration of adjuvant treatment for low risk stage III CC were more often medical oncologists (58% versus 35%, P=0.009) or working in a general hospital (48% versus 22%, P=0.001); no significant difference was observed considering years of professional experience or the number of patients treated per year. For high risk stage III CC (T4 and/or N2), 99.5% of responders considered that adjuvant chemotherapy should be prescribed for 6 months, and 94% with FOLFOX. ConclusionsOne year after the publication of the IDEA study, 3 months of adjuvant chemotherapy with CAPOX has been mainly integrated as a new standard of care for low risk stage III CC patients in daily practice whereas 6 months of FOLFOX remains the standard of care of high risk stage III CC. Legal entity responsible for the studyGERCOR. FundingHas not received any funding. DisclosureB. Rousseau: Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (institution), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: Gilead; Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.

A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer

Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for precisely predicting CRC heterogeneity. We performed transcriptomic profiling using RNA-seq data generated from the primary tissue samples of 130 CRC patients. A prognostic index (PI) based on recurrence-associated genes was developed and validated in two larger independent CRC patient cohorts (n = 795). The association between the PI and prognosis of CRC patients was evaluated using Kaplan–Meier plots, log-rank tests, a Cox regression analysis and a RT-PCR analysis. Transcriptomic profiling in 130 CRC patients identified two distinct subtypes associated with systemic recurrence. Pathway enrichment and RT-PCR analyses revealed an eleven gene signature incorporated into the PI system, which was a significant prognostic indicator of CRC. Multivariate and subset analyses showed that PI was an independent risk factor (HR = 1.812, 95% CI = 1.342–2.448, P < 0.001) with predictive value to identify low-risk stage II patients who responded the worst to adjuvant chemotherapy. Finally, a comparative analysis with previously reported Consensus Molecular Subgroup (CMS), high-risk patients classified by the PI revealed a distinct molecular property similar to CMS4, associated with a poor prognosis. This novel PI predictor based on an eleven gene signature likely represents a surrogate diagnostic tool for identifying high-risk CRC patients and for predicting the worst responding patients for adjuvant chemotherapy.

Postoperative Single-Fraction Partial-Breast Irradiation for Stage 0 and I Breast Carcinoma: Results of a Prospective Single Institution Phase I/II Clinical Trial

To assess tolerability, efficacy, quality of life and cosmetic outcomes of a prospective phase I/II trial of single fraction high gradient partial breast irradiation (SFHGPBI) given postoperatively after partial mastectomy in select patients with stage 0/I breast cancers. Postmenopausal women aged ≥50 years with hormone receptor positive, HER2/neu nonamplified pathologic T1N0 or Tis (=< 2cm) N0 breast cancer treated with partial mastectomy with negative histologic margins by at least 2 mm were treated with postoperative SFHGPBI, 20 Gy to the cavity surface while simultaneously prescribing 7 Gy to a planning target volume (PTV) defined as the surgical bed plus 1 cm of surrounding breast tissue. Co-primary endpoints were grade 3+ toxicity per CTCAE v4.0 and ipsilateral breast tumor recurrence (IBTR). Between 2014 and 2018, 50 patients were enrolled and received SFHGPBI. Patients had either stage I (n=40) or stage 0 (n=10) breast carcinomas. Mean heart dose was 0.43 Gy (range, 0.07 – 1.52 Gy), and maximum skin rind dose was 17.87 Gy (range, 8.43 – 28.53 Gy).With a median follow-up of 21 months, one patient developed a non-invasive IBTR in a separate untreated quadrant 18 months after HGPBI. One other patient developed an ipsilateral axillary recurrence 30 months after HGPBI. There have been no recurrences in the treated quadrant or distantly, with no intercurrent deaths observed. No grade 3-5 toxicities have been observed. All but 3 toxicities have been grade 1, with 17 patients (34%) having small areas of hyperpigmentation in the treatment region, 9 patients having grade 1 fibrosis, and 9 patients having transient breast pain. Grade 2 fibrosis and grade 2 chest wall pain was observed in 2 and 1 patients, respectively. Patient-reported quality of life (QOL) data per EORTC QLQ-30 and QLQ-BR23 collected at baseline and at each follow-up revealed that SFHGPBI had no detrimental effect on overall QOL as well as each of the sub-domains evaluated. Quantitative cosmetic evaluation using the percentage of breast retraction assessment (pBRA) revealed that there was a trend toward improvement in pBRA at 8 weeks (mean, 7.25%) and 12 months (6.97%) post-RT, compared to pretreatment pBRA (8.26%). The rates of good-to-excellent cosmesis reported by patients and the treating physician were 98% and 100% pretreatment, 98% and 100% at 8 weeks, and 100% and 100% at 1 year, respectively. SFHGPBI is a feasible, convenient, and well-tolerated method for delivering adjuvant radiation in patients with low-risk stage 0 and I breast cancers. No grade 3+ toxicity was observed, with low rates of acute adverse events. SFHGPBI had no detrimental effect on patient-reported quality of life, and both patient and physician-reported qualitative and quantitative cosmesis was preserved. Initial local, regional, and distant control rates were excellent.

Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia

Endometrial intraepithelial neoplasia, also known as complex atypical hyperplasia, is a precancerous lesion of the endometrium associated with a 40% risk of concurrent endometrial cancer at the time of hysterectomy. Although a majority of endometrial cancers diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low risk and low stage, approximately 10% of patients ultimately diagnosed with endometrial cancers will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, few data exist regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology. To determine whether preoperative factors can predict the presence of concurrent endometrial cancer at the time of hysterectomy in patients with endometrial intraepithelial neoplasia; and to describe the ability of preoperative characteristics to predict which patients may be at a higher risk for lymph node involvement requiring lymph node assessment at the time of hysterectomy. We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring lymphadenectomy. Unadjusted associations between covariates and progression to endometrial cancer were estimated by 2-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation. Of the 1055 charts reviewed, 169 patients were eligible and included. Of these patients, 87 (51.5%) had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease, whereas 82 (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at the time of hysterectomy (15.7 mm; standard deviation, 9.5) versus 12.5 mm; standard deviation, 6.4; P= .01). An endometrial stripe of ≥2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% confidence interval, 1.5-10.0), controlling for age. In all, 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe of ≥2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe of <2 cm. Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment.

Patterns of adjuvant therapy and outcomes in the treatment of stage II endometrial cancer: A National Cancer Database study

Objective: Currently, use of adjuvant radiation (RT) via brachytherapy or pelvic RT is recommended for patients with surgically staged, low-risk stage II disease with the option of adding chemotherapy (CT) for high-risk disease. However, these recommendations are based on small numbers of stage II EC patients within larger randomized clinical trials or small retrospective reviews. The purpose of this study was to explore patterns of adjuvant therapy and outcomes in a large retrospective cohort of stage II EC patients.

Does mismatch repair (MMR) deficiency have prognostic significance in low-risk endometrioid endometrial cancers?

e17122 Background: Mismatch repair (MMR) deficiency is observed in 25-30% of all endometrial cancers. This can be detected by the absence of MMR protein staining on immunohistochemistry (IHC), and is used in many jurisdictions as a screen for an inherited mutation in one of the MMR genes (Lynch Syndrome). Only 10% of women with MMR deficiency (MMRd) have Lynch syndrome, but MMRd may still have prognostic significance. The objective of this study was to compare clinical outcomes between MMR deficient and proficient low-risk endometrioid endometrial cancers (stage IA, grade 1/2). Methods: This was a retrospective population-based cohort study of all low-risk endometrial cancers from Vancouver Coastal Health authority region from 2011 to 2016 that were assessed for MMR deficiency (MMRd). Primary outcome measures were recurrence rates expressed per person-years (py), progression free survival (PFS) and overall survival (OS) calculated using Kaplan-Meier method and log-rank tests. Cox proportional hazards model estimated the association between MMRd and recurrence and death after adjustment for covariates, expressed as hazard ratios (HR). Results: There were 475 low-risk patients, including 131 MMRd (27.6%) and 345 MMRp (proficient) patients. Women with MMRd tumors had higher recurrence rates (3.53p100py vs 1.21p100py) and worse PFS (p = 0.0082) compared to women with MMRp tumors. After adjustment for age, LVSI status, adjuvant therapy, and post-operative grade, MMRd status remained associated with a higher risk of recurrence (HR 2.99, 95% CI 1.27-7.04). There was no significant difference in OS between MMR groups (HR 1.38, 95% CI 0.57-3.33). Conclusions: In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, MMR deficiency is associated with a higher recurrence rate than in MMR proficient cases, after adjustment for covariates, implying that MMR deficiency reflects a different biology in endometrial cancer.

Utility of the relative apparent diffusion coefficient for preoperative assessment of low risk endometrial carcinoma

ObjectivesLymphadenectomy is not recommended for low risk stage I endometrial carcinoma (EC) patients. This study was to investigate the predictive value of apparent diffusion coefficient (ADC) values in predicting patients with low risk EC, and to identify an optimum ADC measurement for preoperative assessment. Materials and methodsEighty-one patients with stage I EC who underwent diffusion-weighted imaging (DWI) at 1.5T were included and divided into low group and intermediate-high risk group based on the ESMO-ESGO-ESTRO classification. Clinical indexes, conventional MRI parameters, minimum ADC values (minADC), mean ADC values (meanADC) and relative ADC values (rADC) were compared between those two groups. rADC was calculated using the equation ADC (cancer)/ADC (reference) with the obturator internus muscle as reference. The optimal ADC measurement and cut-off ADC value for low risk EC were calculated using the receiver operating characteristic (ROC) curve. ResultsThe low risk group had significantly higher meanADC, minADC, and rADC values than did the intermediate-high risk group (1.095 vs. 0.902 × 10−3 mm2/s, 0.755 vs. 0.657 × 10−3 mm2/s, 0.754 vs. 0.603, respectively). In assessments of low risk EC patients, the area under the curve (AUC) values for meanADC, minADC, and rADC were 0.840 (95%CI, 0.749,0.931), 0.681 (95% CI: 0.561,0.800), and 0.876(95% CI: 0.798,0.954), respectively. The optimal cut-off rADC value for prediction was 0.669, the maximum Youden index, sensitivity, specificity, and accuracy values were 0.683, 81.8%, 86.5%, and 84.0%, respectively. ConclusionsrADC is superior to minADC and meanADC for predicting patients with low risk EC, and could potentially aid to the surgical management of these patients in avoiding unnecessary lymphadenectomy.

Long-term outcome and pattern of failure for patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

To analyze the long-term outcome and pattern of failure for patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Patients with NPC after IMRT from 2001 to 2008 were recruited (n = 865). Clinical features, laboratory data, and treatments were collected. The 10-year local recurrence-free survival, distant metastasis-free survival, and disease-specific survival (DSS) were 92.0%, 83.4%, and 78.6%, respectively. A total of 209 patients died: 59% of whom died from distant metastasis. The 10-year DSS was higher in patients who received chemoradiotherapy than those who received IMRT alone for patients with high-risk stage III disease, while there was no survival difference for patients with stage II and low-risk stage III disease. IMRT provides satisfactory long-term survival for patients with NPC. Distant metastasis has been the most common reason for failure. Adding chemotherapy did not improve survival in patients with stage II and low-risk stage III disease.

Postoperative Single-Fraction Partial Breast Irradiation for Low-Risk Stage 0 and I Breast Carcinomas: Results of a Prospective Clinical Trial

Postoperative Single-Fraction Partial Breast Irradiation for Low-Risk Stage 0 and I Breast Carcinomas: Results of a Prospective Clinical Trial

Efficacy of concurrent chemoradiotherapy combined with nimotuzumab for low-risk T4 stage nasopharyngeal carcinoma: A pilot study.

Background:The purpose of this study was to analyze the efficacy and safety of concurrent chemoradiotherapy combined with Nimotuzumab for low-risk T4 stage nasopharyngeal carcinoma (NPC).Methods:This study included 49 low-risk T4 stage NPC patients treated with concurrent chemoradiotherapy plus Nimotuzumab. The IMRT doses were planning target volume (PTV) 70–72 Gy for gross disease in the nasopharynx, and 66–70 Gy for positive lymph nodes. The doses for high risk and low risk region PTV were 60–62 Gy and 54–56 Gy in 31-33 fractions. All patients received a chemotherapy program consisting of Cisplatin 100mg/m2, day 1, Q3w and were treated by Nimotuzumab (Nimotuzumab 200mg, iv, Qw).Results:All 49 patients completed at least two cycles of chemotherapy and seven weeks of Nimotuzumab. The total efficiency of therapy was 100.0%. The 3-year overall survival (OS), distant metastasis-free survival (DMFS), local-regional control (LRC) and progression-free survival (PFS) rates were 89.7%, 87.8%, 97.9% and 85.7%, respectively. No regional lymph node recurrence was detected. The most serious acute toxicity was mucositis, with prevalence of Grades 0 to IV being 0.0%, 57.1%, 34.7%, 8.2%, and 0.0%, respectively. Late toxicity manifested as Grades I and II xerostomia in 32 and 10 patients.Conclusion:In patients with low-risk T4 stage NPC, concurrent chemoradiotherapy combined with Nimotuzumab yielded an excellent local control rate, and the toxicities were mild and tolerable. Distant metastasis was the main cause of treatment failure.

Trends in the epidemiology of chronic kidney disease in Russian Federation according to the Federal Diabetes Register (2013–2016)

BACKGROUND: Chronic kidney disease (CKD) is one of the most severe complications of diabetes mellitus (DM), this determines the importance of the study of epidemiological characteristics of the disease.&#x0D; AIMS: To assess the epidemiological characteristics of CKD in adult DM patients with type 1 (T1), 2 (T2) in Russian Federation in 201316.&#x0D; METHODS: We have used the database of the Russian Federal Diabetes register, 81st regions included in online register. Indicators were estimated per 10,000 adult DM patients (18years).&#x0D; RESULTS: In 2016, the CKD frequency registration was T1 23%, T2 6.9% with marked interregional differences 1.5-49.9%, 0.623.5%, respectively. The CKD prevalence in dynamics 20132016 was 2171.42303.0 in T1 and 512.687.2 in T2. The incidence of new CKD cases increased 2 times in T1 (215.5 vs 104.2), and 3.7 times in T2 (190.4 vs 51.8). The analysis of distribution by CKD stages by KDIGO indicates the increase in the proportion of patients with low and moderate cardiovascular risk and end stage renal disease (ESRD) (with the initial stages of CKD, C1/2 A1) - 12.046.8% in T1; 10.050.4% in T2. The proportion of patients with a very high risk (stages C4/5 C3aA3 and C3bA2-3) progressively decreases: 13.46.7% in T1, 11.34.4% in T2. We observed relation between the CKD prevalence and DM duration. CKD develops in 5.1% patients if T15 years and in 48.0% if T130years; in T2 3.5% and 20.3%, respectively. The average age of CKD onset in T1 increased for 4,3yr (36,140,2), in T2 for 2,4yr (64,466,8), DM duration until CKD development increased in T1 11.814.2yr, in T2 7.68.2yr.&#x0D; CONCLUSIONS: There is a significant improvement in the quality of CKD diagnostics at the earlier stages, older age and a longer DM duration before CKD onset in both types while we observed the increasing trends in CKD prevalence in Russian Federation in the dynamics of 2013-2016. Advances in the management of patients with DM in recent years do not reduce the risk of CKD, but give us a delay in its development. The marked interregional differences frequency of registration of CKD might indicate some remaining problems in verification in a number of regions where the standard for mandatory assessment of albuminuria and glomerular filtration rate not implemented.

Prognostic Value of a Long Non-coding RNA Signature in Localized Clear Cell Renal Cell Carcinoma

BackgroundLong non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer. ObjectiveWe sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC). Design, setting, and participantsBased on the RNA-seq data of 444 stage I–III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I–III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I–III ccRCC. Outcome measurements and statistical analysisUnivariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival. Results and limitationsUsing the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03–1.75; p=0.028] to 1.89 [95% CI, 1.55–2.31; p<0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II–III patients. ConclusionsThe RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I–III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management. Patient summaryThe RCClnc4 classifier could facilitate patient management and treatment decisions.

Chemo-Radiation After Upfront Rectal Resections-a Clinical Dilemma.

To compare the impact of adjuvant chemo-radiotherapy (ACRT) versus adjuvant chemotherapy (ACT) alone on recurrence and survival in patients with stage II and III rectal adenocarcinoma undergoing upfront curative resection. Prospective observational review of colorectal database at Tata Memorial Hospital from July 2010 to March 2015 identified 84 patients who underwent upfront curative resection for stage II or III rectal cancer. None of the patient received preoperative chemo-radiation. Of these, adjuvant chemo-radiotherapy was administered to 29 patients (ACRT group) and 55 patients received CAPEOX/FOLFOX-based adjuvant chemotherapy (ACT group) alone. At a median follow-up of 20months, there were 10 recurrences (3 local recurrence) in the ACRT group and 15 (2 local recurrence) in ACT group. The estimated disease-free survival at 3years in the ACRT group was 62.7% and in ACT group was 49.7% (p = 0.417) with an estimated 3-year overall survival of 74 and 78% in the ACRT and ACT group, respectively (p = 0.241). Subgroup analysis was performed after risk stratifying prognostic features (pT4, pN2, poor differentiation, involved resection margin). Our study does not show any benefit of ACRT over ACT on local control, disease-free and overall survival after upfront rectal cancer resection for low-risk stage II-III. In the subgroup analysis, local recurrence did not occur in patients who did not have poor prognostic features irrespective whether they received ACRT or ACT. Adjuvant chemo-radiation can be avoided in low-risk stage II-III rectal cancer after upfront resection.