Prognostic Factor For Disease-specific Survival Research Articles

Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis.

To compare clinical characteristics, surgical and oncologic outcomes of clear cell ovarian cancer among patients with cancer arising from endometriosis, cancer coexisting with endometriosis, and cancer without endometriosis. A retrospective chart review of patients diagnosed with clear cell ovarian cancer during January 1998-March 2013 was performed. All histopathology specimens were reviewed by a gynecologic pathologist and classified into one of the three following endometriosis status groups: arising group, coexisting group, or without group. The primary outcome was disease-specific survival (DSS). The secondary outcomes were progression-free survival, surgical morbidities, response rate, recurrence rate, and cancer-specific death. Finally, 249 patients were included. There were 82, 96, and 71 patients in the arising, coexisting, and without groups, respectively. Regarding baseline characteristics among groups, the without group was significantly older and had more advanced diseases. There was a significant difference in progression-free survival between the arising group and the without group (p = 0.003). Five-year progression-free survival rates were 62.8% in the arising group, 50.2% in the coexisting group, and 38.3% in the without group. DSS was not significantly different among groups. Multivariate analysis revealed ovarian surface invasion (HR = 2.76) and pelvic lymphadenectomy (HR = 0.39) to be independent prognostic factors for progression-free survival, whereas no remission after primary treatment (HR = 8.03) and pelvic lymphadenectomy (HR = 0.21) were prognostic factors for DSS. Intraoperative blood loss and residual tumor were significantly higher in the without group. Endometriosis status was found not to significantly influence surgical and oncologic outcomes in patients with clear cell ovarian cancer.

Prognostic impact of dimensional factors in pT1 gastric cancer

BackgroundThe significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer. ObjectivesThis study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer. MethodsWe analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve. ResultsCox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival. ConclusionsThe dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies.

Benefit of postoperative radiotherapy in patients with oropharyngeal squamous cell carcinoma in human papillomavirus (HPV) era: A Surveillance, Epidemiology, and End Results (SEER) database analysis

BackgroundThis study aimed to investigate the survival benefit of postoperative radiotherapy in patients with resected human papilloma virus-positive oropharyngeal squamous cell carcinoma using data from the Surveillance, Epidemiology, and End Results database. MethodsA total of 2,589 human papilloma virus-positive oropharyngeal squamous cell carcinoma patients who underwent surgery were identified from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics between patients who received postoperative radiotherapy and those who did not. Overall survival and disease-specific survival were estimated. ResultsAfter propensity score matching, postoperative radiotherapy did not increase overall survival and disease-specific survival. The subgroup analysis revealed that overall survival and disease-specific survival benefits of postoperative radiotherapy were observed only among patients with N2 or N3 stage disease. Multivariate analysis revealed that old age and advanced T, N stages were prognostic factors for disease-specific survival in oropharyngeal squamous cell carcinoma patients who underwent surgery. ConclusionPostoperative radiotherapy might improve the survival of human papilloma virus-positive oropharyngeal squamous cell carcinoma patients with advanced N stage.

Spermatic Cord Sarcoma: A 20-Year Single-Institution Experience.

Introduction: Spermatic cord sarcomas represent a rare genitourinary malignancy with a challenging diagnostic and therapeutic pathway. Different histotypes have been described and prognostic factors remain poorly defined due to the paucity of data presented in literature.Methods: Retrospective chart review of 22 adult patients treated for spermatic cord sarcoma in a single institution in the last 20 years was performed. Clinicopathological characteristics of the tumors were collected with primary and subsequent treatment. Survival analysis was performed in order to identify prognostic factors of disease-specific survival.Results: The median age at diagnosis was 68 years (58–78), the most common histotype was liposarcoma (14/22), and most patients (63.6%) were found to have positive surgical margins after surgery. The 5-year cancer specific survival was 91.3%. Grading (p = 0.480), histotype (p = 0.327), and type of intervention (p = 0.732) were not associated with survival. All patients dead of disease had positive surgical margins (p = 0.172).Conclusion: We report a good prognosis at 5 years. Wide radical resection remains the first and probably the most important step; thus, according also to literature, negative surgical margins should be aimed.

Prognostic factors of metastatic myxoid liposarcoma

BackgroundMyxoid liposarcoma (MLS) has the tendency to metastasize extrapulmonary. Although prognostic factors at the initial diagnosis of MLS have been reported, those at diagnosis of metastasis remain unclear. The purpose of this study was to investigate the prognostic factors for disease-specific survival at the initial diagnosis of metastasis.MethodsThis retrospective observational study was conducted at three cancer centers and two university hospitals in Japan. Of 274 MLS patients pathologically diagnosed between 2001 and 2015, 48 metastatic patients were examined.ResultsLung metastases were detected in nine patients (18.8%) and extrapulmonary metastases in 45 (93.8%). Interval from primary diagnosis to the first metastasis was significantly shorter in patients with lung metastases than without (p = 0.007). Median disease-specific survival after diagnosis of metastases was 52.5 months in all patients. In multivariable analysis, liver metastasis (hazard ratio (HR), 2.71 [95% confidence interval (CI), 1.00–7.09]) and no evidence of disease (NED) achieved by radical treatment (resection with or without radiation therapy, or radiation therapy ≥60 Gy) or semi-radical (radiation therapy ≥40 Gy) treatment were significantly related to survival (HR, 0.36; 95%CI [0.13–0.95]). The number of metastases (odds ratio (OR), 0.44; 95%CI [0.25–0.78]) and abdominal/retroperitoneal metastases (OR, 0.09; 95%CI [0.008–0.95]) were the significant inhibitory factors of achieving NED.ConclusionsThis is the first study to statistically demonstrate the importance of achieving NED with surgical resection or radiation therapy for longer survival in metastatic MLS patients. As number of metastases was a significant factor for achieving NED, early detection of metastases might be important.

Histological features and survival in young patients with HPV-negative oral squamous cell carcinoma.

The frequency of oral squamous cell carcinoma in young adults has increased in the last decades, and there are conflicting results in literature about its prognosis in young subjects. The aim of this study was to analyse the clinical and pathological features of oral squamous cell carcinoma in a cohort of young adults in order to investigate the presence of new independent prognostic markers. Only HPV-negative young patients (under 40-year-old) affected by oral squamous cell carcinoma were considered in this study. Clinical and pathological data were collected. Patients were re-staged according to the 8th edition of AJCC. Overall, 66 patients were considered in this study. Perineural invasion significant correlated with both 7th and 8th edition of AJCC, and lymphovascular invasion (p-value<.05). The multivariate survival analysis showed that patients with perineural invasion had a significant worse prognosis (HR=6.384 95% C.I. 1.304-31.252; p-value=.022). Perineural invasion emerged as an independent prognostic factor for disease-specific survival in young patients with oral squamous cell carcinoma. Furthermore, the evaluation of this parameter is simple, inexpensive and can be used to augment the risk stratification of oral cancer based on the 8th edition of AJCC.

High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

BackgroundTumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy.MethodsSeventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5).ResultsIn this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001).ConclusionThis study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.

Intraoperative Transfusion is Independently Associated with a Worse Prognosis in Resected Pancreatic Cancer-a Retrospective Cohort Analysis.

Backgrounds: Investigate whether intraoperative transfusion is a negative prognostic factor for oncologic outcomes of resected pancreatic cancer. Methods: From June 2004 to January 2014, the medical records of 305 patients were retrospectively reviewed, who underwent pancreatoduodenectomy, pylorus preserving pancreatoduodenectomy, total pancreatectomy, distal pancreatectomy for pancreatic cancer. Patients diagnosed with metastatic disease (n = 3) and locally advanced diseases (n = 15) were excluded during the analysis, and total of 287 patients were analyzed. Results: The recurrence and disease-specific survival rates of the patients who received intraoperative transfusion showed poorer survival outcomes compared to those who did not (P = 0.031, P = 0.010). Through multivariate analysis, T status (HR (hazard ratio) = 2.04, [95% CI (confidence interval): 1.13–3.68], P = 0.018), N status (HR = 1.46 [95% CI: 1.00–2.12], P = 0.045), adjuvant chemotherapy (HR = 0.51, [95% CI: 0.35–0.75], P = 0.001), intraoperative transfusion (HR = 1.94 [95% CI: 1.23–3.07], P = 0.004) were independent prognostic factors of disease-specific survival after surgery. As well, adjuvant chemotherapy (HR = 0.67, [95% CI: 0.46–0.97], P = 0.035) was independently associated with tumor recurrence. Estimated blood loss was one of the most powerful factors associated with intraoperative transfusion (P < 0.001). Conclusions: Intraoperative transfusion can be considered as an independent prognostic factor of resected pancreatic cancer. As well, it can be avoided by following strict transfusion policy and using advanced surgical techniques to minimize bleeding during surgery.

Prognostic value of risk stratification using blood biochemical parameters in Japanese patients with metastatic renal cell carcinoma treated by nivolumab.

724 Background: Nivolumab is a standard treatment for previously treated advanced renal-cell carcinoma (RCC). However, nivolumab is effective in only a limited number of patients; therefore, we evaluated the prognostic value of several biomarkers, including inflammation-based prognostic scores and changes in these scores following nivolumab treatment in Japanese patients with metastatic RCC. Methods: We retrospectively reviewed the medical records of 65 patients with previously treated metastatic RCC and who received nivolumab. MSKCC and IMDC risk, inflammation-based prognostic scores, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and Glasgow prognostic score before and 6 weeks after the treatment were recorded. Categorical variables influencing disease-specific and overall survival were compared using Cox proportional-hazards regression models. Results: Univariate analysis showed that MSKCC risk score ( P = 0.0052), lactate dehydrogenase (LDH) ( P = 0.0266), LMR ( P = 0.0113), and PLR ( P = 0.0017) had a significant effect on disease-specific survival. Multivariate analyses showed that PLR and LDH were found to be independent prognostic factors for disease-specific survival ( P = 0.0008, RR = 7.95, 95% CI, 2.16–51.64 and P = 0.0123, RR = 3.92, 95% CI, 1.37–10.80, respectively). The combination of PLR and LDH was the most significant prognostic biomarker in metastatic RCC for disease-specific ( P &lt; 0.0001) and overall ( P &lt; 0.0001) survival. Changes in LMR and PLR in response to nivolumab were significant prognostic factors for disease-specific survival ( P &lt; 0.0001 and P = 0.0477, respectively). Conclusions: The combination of PLR and LDH may be a potential biomarker for estimating disease-specific and overall survival in Japanese patients with metastatic RCC treated by nivolumab. If changes of inflammation-based prognostic scores in response to nivolumab treatment might be improved, nivolumab treatment should be continued.

Prognostic Factors in Stage IB Gastric Cancer after Surgical Resection.

PurposeThe standard treatment for stage IB gastric cancer is curative surgery alone, but some patients show poor survival with disease recurrence after curative surgery. The aim of this study was to identify prognostic factors of recurrence and long-term survival in patients with stage IB gastric cancer after surgery.Materials and MethodsWe retrospectively reviewed data from 253 patients with stage IB gastric cancer who underwent gastrectomy between 2011 and 2016 at Kyungpook National University Chilgok Hospital and analyzed the clinicopathological characteristics associated with recurrence and survival.ResultsFourteen patients experienced recurrence with a mean follow-up of 54.1 months. Two of these patients had locoregional recurrence and 12 patients had systemic recurrence. The median interval between the operation day and the day of recurrence was 11 months (range 4–56 months). Multivariate analysis revealed that lymphatic vessel invasion (LVI) (hazard ratio [HR], 3.851; 95% confidence interval [CI], 1.264–11.732) and the elderly (age≥65) (HR, 3.850; 95% CI, 1.157–12.809) were independent risk factors for recurrence after surgery. The LVI (HR, 3.630; 95% CI, 1.105–11.923) was the independent prognostic factors for disease-specific survival (DSS). The 5-year DSS rates were 96.8% in patients who did not have LVI, and 89.3% in patients who had LVI.ConclusionsThis study shows that LVI was associated with recurrence and poor survival in patients with stage IB gastric cancer after curative gastrectomy. Patients diagnosed with LVI require careful attention for systemic recurrence during the follow-up period.

Prognostic value of risk stratification using blood parameters for nivolumab in Japanese patients with metastatic renal-cell carcinoma.

Nivolumab is a standard treatment for previously treated advanced renal-cell carcinoma. However, nivolumab is effective in only a limited number of patients; therefore, we evaluated the prognostic value of several biomarkers, including inflammation-based prognostic scores and changes in these scores following nivolumab treatment in Japanese patients with metastatic renal-cell carcinoma. We retrospectively reviewed the medical records of 65 patients with previously treated metastatic renal-cell carcinoma and who received nivolumab. Inflammation-based prognostic scores, including neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, and Glasgow prognostic score before and 6weeks after the treatment were recorded. Categorical variables influencing disease-specific survival were compared using Cox proportional-hazards regression models. Univariate analysis showed that Memorial Sloan-Kettering Cancer Center risk score (P=0.0052), lactate dehydrogenase (P=0.0266), lymphocyte/monocyte ratio (P=0.0113), and platelet/lymphocyte ratio (P=0.0017) had a significant effect on disease-specific survival. Multivariate analyses showed that platelet/lymphocyte ratio and lactate dehydrogenase were found to be independent prognostic factors for disease-specific survival (P=0.0008, risk ratio (RR)=7.95, 95% confidence interval, 2.16-51.64 and P=0.0123, RR=3.92, 95% confidence interval, 1.37-10.80, respectively). The combination of platelet/lymphocyte ratio and lactate dehydrogenase was the most significant prognostic biomarker in metastatic renal-cell carcinoma (P<0.0001). Changes in lymphocyte/monocyte ratio and platelet/lymphocyte ratio in response to nivolumab were significant prognostic factors for disease-specific survival (P<0.0001 and P=0.0477, respectively). The combination of platelet/lymphocyte ratio and lactate dehydrogenase may be a potential biomarker for estimating disease-specific survival in Japanese patients with metastatic renal-cell carcinoma treated by nivolumab.

Outcome and Prognosis Factors of Stage IV Cervical Cancer Patients: A Decade Experience

The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stages IVA) and metastatic CC (i.e., stages IV). A retrospective review was conducted, based on all consecutive patients treated for stage IV CC in a comprehensive cancer care center between 2004 and 2017. Sixty-eight patients were included. Performance status (PS) was ≥ 2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph nodes metastases (38.6%), 13 had only distant metastases (29.5%) and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n=14, 58.3%) +/- a concomitant chemotherapy, or a palliative treatment (n=10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), eleven a primary concomitant chemoradiation (25%), and ten a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stages IVA (95%CI=0.7-33.9), and 10.5% for stages IVB (95%CI=3.7-29.7). In multivariate analysis, PS>1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS>1 and pelvic lymph nodes involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC. In daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies.

Long-term outcome of rare oncocytic papillary (Hürthle cell) thyroid carcinoma following (adjuvant) initial radioiodine therapy.

Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11% of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. OPTC patients were significantly older (55.2 ± 12.3years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8cm for OPTC patients, 1.5 ± 1.2cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097-1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching.

Retrospective analysis of seven cases of pancreatic mixed adenoneuroendocrine carcinoma from a high-volume center and review of the literature

BackgroundsThe clinicopathologic features and biological behaviors of pancreatic mixed adenoneuroendocrine carcinoma (pMANEC) and its impacts on survival are poorly known.MethodsWe retrospectively reviewed seven pMANEC cases from a single institution from September 2010 to January 2017 along with twenty-one previously reported cases from the literature. Survival and prognostic analyses were conducted using Kaplan-Meier estimates and Cox regression, respectively.ResultsSeven pMANEC cases were identified during the study interval. Among the six patients who underwent operations, five reached R0 resections, one experienced postoperative pancreatic fistula, and two suffered other complications. The median progression-free survival (PFS) and disease-specific survival (DSS) were 7.5 months (2 to 36 months) and 15 months (6 to 36 months), respectively. A total analysis of twenty-eight pMANEC cases showed that patients were mostly older (median age, 59.5 years) and male (64.3%). The two most common symptoms were abdominal pain (53.6%) and obstructive jaundice (35.7%). The majority of pMANECs were non-functional (89.3%) and located in the pancreatic head (64.3%). The median diameter of pMANEC was 3.0 cm, with a wide range (0.5 to 19.0 cm). Lymph node metastasis (P = 0.015) was associated with decreased DSS, while age (P = 0.414), sex (P = 0.125), tumor size (P = 0.392), location (P = 0.913), functional status (P = 0.313), CA19–9 level (P = 0.608), and liver metastasis (P = 0.935) did not show significant prognoses on DSS.ConclusionsWe reported seven pMANEC cases and outlined their clinical behaviors and prognoses with a review of twenty-one cases from the literature. Lymph node metastasis was found to be a negative prognostic factor of DSS based on the present study.

Special Focus on Stage IV Cervical Cancer Patients: A Decade Experience

Objectives: The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stage IVA) and metastatic CC (i.e., stage IVB). Method: A retrospective review was conducted based on all consecutive patients treatedfor stage IV CC in a comprehensive cancer care centre between 2004 and 2017. Results: Sixty-eight patients were included. Performance status (PS) was ≥2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph node metastases (38.6%), 13 had only distant metastases (29.5%), and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n = 14, 58.3%) +/– concomitant chemotherapy, or a palliative treatment (n = 10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), 11 a primary concomitant chemoradiation (25%), and 10 a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stage IVA (95% CI = 0.7–33.9), and 10.5% for stage IVB (95% CI = 3.7–29.7). In multivariate analysis, PS >1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS >1 and pelvic lymph node involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC. Conclusions: In daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies.

Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status

The CD274 (programmed cell death ligand-1, PD-L1)/PDCD1 (programmed cell death-1, PD-1) pathway is crucial suppressor of the cytotoxic immune response. Antibodies targeting CD274 or PDCD1 have been revealed to be effective in several malignancies. In colorectal cancer, the response to CD274/PDCD1 blockage is associated with microsatellite instability. However, the value of CD274/PDCD1 for predicting response to treatment or survival benefit is still unclear. The aims of the study were (1) to clarify differences in immune microenvironment and expression of checkpoint proteins (CD274/PDCD1) in DNA mismatch repair-proficient, mismatch repair-deficient, and hereditary Lynch syndrome-associated colorectal cancer, and (2) to assess the prognostic value of these factors and their combinations. Ninety-four mismatch repair-deficient colorectal cancers, 100 age, sex, and AJCC/UICC stage-matched mismatch repair-proficient colorectal cancers, and 48 Lynch syndrome-associated colorectal cancers were analyzed. Using whole section samples, detailed analysis of immune cell score, PDCD1, and CD274 expression was performed. Overlapping of CD274 expression in tumor and immune cells was almost complete (95%). Immune cell score and CD274/PDCD1 positivity were significantly more frequent in mismatch repair-deficient than in mismatch repair-proficient colorectal cancers (70% vs. 41% (high immune cell score); 81% vs. 49% (PDCD1high), 23% vs. 1% (CD274 on tumor cells) and 68% vs. 30% (CD274 on immune cells), P < 0.001), and were associated strongly with each other. Although the independent impact of immune cell score, PDCD1, and CD274 on immune cells was moderate, the immunoprofile parameter combining the above three factors appeared to be a strong independent prognostic factor for disease-specific survival and overall survival (P = 0.001) and had suggestive impact on disease-free survival (P = 0.011). Our results encourage the use of immune cell score analysis together with PDCD1 and CD274 detection to improve the prognostic evaluation of colorectal cancer patients. Particularly, the analyses from whole tissue sections are encouraged to allow reliable and cell-specific analyses of CD274 expression.

Tumour necrosis as assessed with 18F-FDG PET is a potential prognostic marker in diffuse large B cell lymphoma independent of MYC rearrangements

ObjectivesMYC gene rearrangements in diffuse large B cell lymphomas (DLBCLs) result in high proliferation rates and are associated with a poor prognosis. Strong proliferation is associated with high metabolic demand and tumour necrosis. The aim of this study was to investigate differences in the presence of necrosis and semiquantitative 18F-FDG PET metrics between DLBCL cases with or without a MYC rearrangement. The prognostic impact of necrosis and semiquantitative 18F-FDG PET parameters was investigated in an explorative survival analysis.MethodsFluorescence in situ hybridisation analysis for MYC rearrangements, visual assesment, semiquantitative analysis of 18F-FDG PET scans and patient survival analysis were performed in 61 DLBCL patients, treated at a single referral hospital between 2008 and 2015.ResultsOf 61 tumours, 21 (34%) had a MYC rearrangement (MYC+). MYC status was neither associated with the presence of necrosis on 18F-FDG PET scans (necrosisPET; p = 1.0) nor associated with the investigated semiquantitative parameters maximum standard uptake value (SUVmax; p = 0.43), single highest SUVmax (p = 0.49), metabolic active tumour volume (MATV; p = 0.68) or total lesion glycolysis (TLG; p = 0.62). A multivariate patient survival analysis of the entire cohort showed necrosisPET as an independent prognostic marker for disease-specific survival (DSS) (HR = 13.9; 95% CI 3.0–65; p = 0.001).ConclusionsMYC rearrangements in DLBCL have no influence on the visual parameter necrosisPET or the semi-quantiative parameters SUVmax, MATV and TLG. Irrespective of MYC rearrangements, necrosisPET is an independent, adverse prognostic factor for DSS.Key Points• Retrospective analysis indicates that MYC rearrangement is not associated with necrosis on18F-FDG PET (necrosisPET) scans or semiquantitative18F-FDG PET parameters.• NecrosisPETis a potential independent adverse prognostic factor for disease-specific survival in patients with DLBCL and is not influenced by the presence of MYC rearrangements.

Survival and Long-Term Biochemical Cure in Medullary Thyroid Carcinoma in Denmark 1997-2014: A Nationwide Study.

Background: Survival of medullary thyroid carcinoma (MTC) subgroups in relation to the general population is poorly described. Data on the factors predicting long-term biochemical cure in MTC patients are nonexistent at a population level. A nationwide retrospective cohort study of MTC in Denmark from 1997 to 2014 was conducted, aiming to detect subgroups with survival similar to that of the general population and to identify prognostic factors for disease-specific survival and long-term biochemical cure.Methods: The study included 220 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. As a representative sample of the general population, a reference population matched 50:1 to the MTC cohort was used.Results: Patients diagnosed with hereditary MTC by screening (hazard ratio [HR] = 1.5 [confidence interval (CI) 0.5–4.3]), patients without regional metastases (HR = 1.4 [CI 0.9–2.3]), and patients with stage I (HR = 1.3 [CI 0.6–3.1]), stage II (HR = 1.1 [CI 0.6–2.3]), and III (HR = 1.3 [CI 0.4–4.2]) disease had an overall survival similar to the reference population. On multivariate analysis, the presence of distant metastases (HR = 12.3 [CI 6.0–25.0]) predicted worse disease-specific survival, while the absence of regional lymph node metastases (odds ratio = 40.1 [CI 12.0–133.7]) was the only independent prognostic factor for long-term biochemical cure.Conclusions: Patients with hereditary MTC diagnosed by screening, patients without regional metastases, and patients with stages I, II, and III disease may have similar survival as the general population. The presence of distant metastases predicted worse disease-specific survival, while the absence of regional metastases predicted long-term biochemical cure.

Dysregulation of ß‐catenin, WISP1 and TCF21 predicts disease‐specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck

The objective of this study was to determine the prognostic and predictive impact of β-catenin, TCF21 and WISP1 expression in patients with squamous cell carcinomas of the head and neck who underwent primary radiotherapy or concomitant chemoradiotherapy. Prospective cohort study. University hospital. Protein expression profiles of β-catenin, TCF21, WISP1 and p16 were determined by immunohistochemical analyses in tissue samples of 59 untreated patients. Expression was correlated with different outcome parameters. Impact of TNM classification, grading, sex, age, gender, type of therapy, response to therapy and p16 status on disease-specific (DSS) and disease-free survival (DFS). Patients with high expression of TCF21 were associated with significantly worse disease-specific survival (P=0.005). In a multivariable analysis, TCF21 was a significant determinant of disease-specific survival. (HR 3.01; P=0.036). Conversely, low expression of β-catenin (P=0.025) and WISP1 (P=0.037) revealed a better response to radiotherapy. Since data show that TCF21 is a prognostic factor for disease-specific survival and WISP1 and ß-catenin are predictive factors for clinical outcome after definitive radiotherapy, further studies are warranted to prove these preliminary but very promising findings.

Importance of tumor budding grade as independent prognostic factor for early tongue squamous cell carcinoma.

Factors involved in neck lymph node metastasis (NLM) and prognosis of early tongue squamous cell carcinoma (SCC) remain unknown. We analyzed disease-specific survival (DSS) and NLM including tumor budding grade (TBG) among 64 patients with cT1/2N0 tongue SCC. Univariate analysis of DSS of primary lesions uncovered significant differences in new cT, pT, new pT, pDiameter, venous infiltration, and TBG. Multivariate analysis selected only TBG3 as a predictor of NLM (odds ratio, 9.55; 95% confidence interval [CI], 1.80-50.8; P = .008), and a prognostic factor for DSS (hazard ratio, 4.41; 95% CI, 1.34-14.5; P = .02). The sole predictor of NLM and the prognosis of early tongue SCC was TBG, indicating that it might help to select overwhelming risk patients.