Significant Prognostic Factors For Overall Survival Research Articles

Postoperative Survival in Colitis-associated Colorectal Cancer With Ulcerative Colitis in Japan: A Multicenter Analysis

The aim of the study was to analyze the postoperative survival of colitis-associated colorectal cancer (CAC) with ulcerative colitis (UC), and the risk factors affecting it. A questionnaire including postoperative survival was sent to 88 hospitals that reported CAC patients in the literature up until January, 2006 and to members of the Research Group of Intractable Inflammatory Bowel Disease. The 5-year postoperative overall survival (OS) of 170 CAC patients was 74.2% which was similar to sporadic colorectal cancer in Japan (72.1%). Pathologic TNM stage, histological type, type of surgical procedure (proctocolectomy, segmental resection), and preoperative cancer surveillance were statistically significant factors for OS. By Cox regression analysis, pathologic TNM stage and proctocolectomy were statistically significant prognostic factors for OS. In CAC with UC, the postoperative OS was similar to sporadic colorectal cancer. Pathologic TNM stage and proctocolectomy were confirmed as important prognostic factors.

Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer

PurposeTo evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). Patients and methodsA pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. ResultsIn the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3–3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1–3.0] for OS and 1.7 [1.1–2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). ConclusionThe findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.

Malignant Transformation in Vestibular Schwannoma: Clinical Study With Survival Analysis

AimVestibular schwannomas (VSs) are generally considered benign tumors, and malignant transformation of VSs (MTVSs) are rare findings. The clinical features, treatment strategy, outcomes and prognostic factors remain unclear. We endeavored to analyze the natural history, management, outcomes and prognostic factors of MTVSs.Materials and MethodsThe clinical features, radiologic findings, pathological investigations and surgical outcomes of 4 patients with MTVSs treated at the authors’ institution between 2010 and 2019 were retrospectively collected. Related literature published until December 2019 (63 articles, 67 patients) was evaluated. The authors also made a pooled analysis to evaluate the risk factors for overall survival (OS) time.ResultsOf the 4 cases in our series, 3 cases were malignant transformation following previous treatment (surgery and radiosurgery) and 1 was primary MTVS. Of the 71 MTVSs from the literature, 27 were male and 39 were female, with the mean age of 47.2 ± 17.5 years old. Twelve patients (18.5%) were diagnosed with NF2 (15.4%) or NF1 (3.1%). Forty-three (61.4%) patients underwent previous treatment (surgery and/or radiotherapy) prior to the pathological diagnosis of MTVSs. The mean size of the MTVSs was 35.1 ± 13.2mm. The mean Ki-67 index was 30.6% ± 18.8%. Twenty-four (49.0%) patients underwent gross total resection, 25 (51.0%) patients underwent incomplete resection. Twenty-five (44.6%) underwent adjuvant radiotherapy (RT) postoperatively. During the average follow-up of 9.9 ± 9.5 months (range, 0-40 months), 37 (82.2%) patients developed a local recurrence or metastasis. Forty-seven (73.4%) patients died of tumor progression or postoperative complications. The overall 1-year and 2-year survival rate was 42.3% and 18.6% respectively. Log-rank testing for Kaplan-Meier survival analysis identified that size (P = 0.047) and adjuvant radiotherapy (P=0.001) were significant prognostic factors for OS. Multivariate analysis revealed that adjuvant RT was the only prognostic factor for longer OS (P = 0.005).ConclusionsMTVSs are rare, fatal disease, prone to recur and metastasize rapidly, resulting in death in most of the cases. We found that GTR did not improve the survival in MTVSs but postoperative adjuvant RT can significantly improve the OS, and we recommend early postoperative RT in MTVSs regardless of extent of resection.

High Serum Alkaline Phosphatase Flare after First-Line Androgen Deprivation Therapy Predicts Poor Prognosis in Metastatic Prostate Cancer Patients Treated with Second-Generation Androgen Receptor Targeted Therapy.

Objectives To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. Methods One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. Results The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio (p=0.0367). However, no difference was seen between a high and low ALP flare ratio (p=0.8054) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS (p < 0.0001). Conclusions A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision.

BIMG-06. RESPONSE ASSESSMENT OF BEVACIZUMAB THERAPY FOR GLIOBLASTOMA BY USING MULTIPLE PET TRACERS

OBJECTIVEUse of the positron emission tomography (PET), such as 18F-fluorodeoxyglucose (FDG), 11C-Methionine (MET), 18F- Fluorothymidine (FLT), and 18F-Fluoromisonidazole (FMISO), is expected to lead the way for novel applications aimed at achieving efficient malignancy grading and treatment of gliomas. The aim of this study was to assess FDG, MET, FLT, and FMISO PET studies to evaluate the biological effects induced by bevacizumab (BEV) therapy in glioblastoma patients.METHODSSeventy-one patients with glioblastoma were treated biweekly with BEV from July 2013 to November 2020. FDG, MET, FLT, and FMISO PET scans were obtained at baseline and at follow-up (4 weeks after treatment onset). Measures of FDG, MET, FLT, and FMISO avidity were recorded; the measures were SUVmax, metabolic tumor volume (MTV; volume of tumor with SUV>42% of SUVmax), SUVmean (within the MTV), tumor-to-normal ratio (TNR), tumor-to blood ratio (TBR), and total lesion avidity (TLA; calculated as MTV x SUVmean). The prognostic analysis was performed in relation to the response assessment by multiple PET tracers using progression-free survival (PFS) and overall survival (OS).RESULTSUnder the assessment of the Cox proportional hazard model, increased changes of FDG SUVmax, MET TLA at follow-up, FLT TLA at follow up, increased changes of FLT TLA, increased changes of FMISO TBR and FMISO MTV were significant prognostic factor of PFS. Increase changes of FDG TLA and FLT TLA and increased changes of FMISO TBR were significant prognostic factor of OS.CONCLUSIONIncreased changes in FLT TLA and FMISO-PET after BEV therapy may be a useful biomarker for predicting PFS and OS in glioblastoma.

The Impact of Prolonged Mechanical Ventilation on Overall Survival in Patients With Surgically Treated Brain Metastases

ObjectiveSurgical resection represents a common treatment modality in patients with brain metastasis (BM). Postoperative prolonged mechanical ventilation (PMV) might have an enormous impact on the overall survival (OS) of these patients suffering from advanced cancer disease. We therefore have analyzed our institutional database with regard to a potential impact of PMV on OS of patients who had undergone surgery for brain metastases.Methods360 patients with surgically treated brain metastases were included. The definition of PMV consisted of postoperative mechanical ventilation lasting for more than 48 hours. Analysis of survival incorporating established prognostic factors such as age, location of BM, and preoperative physical status was performed.Results14 of 360 patients with BM (4%) suffered from postoperative PMV after surgical treatment of BM. Patients with PMV presented in a significantly more impaired neurological condition preoperatively than patients without (p<0.0001). Multivariate analysis determined PMV to be a significant prognostic factor for OS after surgical treatment in patients with BM, independent of other predictive factors (p<0.0001).ConclusionsThe present study demonstrates postoperative PMV as significantly related to poor OS in patients with surgically treated BM. Postoperative PMV is a so far underestimated prognostic predictor, but might be utilized for optimized patient management early in the postoperative phase. For this purpose, the results of the present study should encourage the initiation of further scientific efforts.

Prognostic Value of Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA 19-9) in Gallbladder Cancer; 65 IU/mL of CA 19-9 Is the New Cut-Off Value for Prognosis.

Simple SummaryGallbladder cancer (GBC) is the fifth most common cancer of the digestive tract, and preoperative tumor markers for GBC have been studied as a less invasive way to detect the presence of the cancer. CEA and CA 19-9 have been most commonly used for detecting GBC clinically, and various cut-off values were suggested to satisfy this purpose, but there has still been a lack of proper values of these tumor markers to predict the prognosis of GBC. We have aimed to suggest appropriate cut-off values that could help to anticipate prognosis in the preoperative period. Data from carefully selected 539 patients were used in our study, the new cut-off value, 65 IU/mL for CA 19-9 was derived through an up-to-date statistical method. By using this cut-off value, clinicians could get the important reference in the establishment of the strategy of treatment, and the researches about this topic could become more vigorous.Due to the lack of appropriate tumor markers with optimal cut-off values to predict the prognosis of gallbladder cancer (GBC), this study aimed to demonstrate the relationship between prognosis and the levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), and to determine optimal thresholds. In total, 539 patients diagnosed with GBC were examined. The relationship between tumor marker levels and overall survival (OS) was analyzed. The C-tree method was used to suggest tumor marker thresholds, and multivariate analysis was conducted to identify prognostic factors for overall survival. The mean age of the patients was 65.3 years, and the 5-year overall survival rate in all patients was 68.9%. Following the C-tree method, the optimal cut-off value was set at 5 IU/mL for CEA and at 65 IU/mL for CA 19-9. Multivariate analysis revealed that age, CA 19-9 level, operative method, T stage, and N stage were significant prognostic factors for OS. Consequently, CA 19-9 had a stronger association with prognosis than CEA, and 65 IU/mL for CA 19-9 may be suggestive in evaluating the prognosis of GBC. Moreover, it could be an effective indicator for determining the surgical extent necessary and the need for adjuvant treatment.

Clinical Benefits of Conversion Surgery for Unresectable Pancreatic Ductal Adenocarcinoma: A Single-Institution, Retrospective Analysis.

Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is a dismal disorder, but conversion surgery (CS) has provided possibilities of better prognosis for unresectable (UR-)PDAC. We retrospectively investigated the clinical benefits of CS in patients with UR-PDAC. We performed CS in 20 of the 398 UR-PDAC cases between 2006 and 2019(5.1%). Compared the overall survival (OS) period among patients undergoing CS, resectable (R), borderline resectable (BR), unresectable locally advanced cancer (UR-LA), and unresectable cancer with distant metastasis (UR-M) groups, the CS group had significantly better survival than R, BR, UR-LA, and UR-M groups (73.7, 32.7, 22.7, 15.7, and 8.8 months, respectively). Moreover, multivariate analysis revealed the presence of chemoraiotherapy and partial response/complete response in the Response Evaluation Criteria in Solid Tumors (RECIST) were statistically significant prognostic factors for OS among patients undergoing CS (p = 0.004 and 0.03, respectively). This study highlights importance of multidisciplinary treatment including CS for patients with UR-PDAC.Background: Unresectable pancreatic ductal adenocarcinoma (UR-PDAC) has a poor prognosis. Conversion surgery is considered a promising strategy for improving the prognosis of UR-PDAC. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PDAC. Methods: We retrospectively evaluated patients with PDAC who were referred to our department for possible surgical resection between January 2006 and December 2019. Conversion surgery was performed only in patients with UR-PDAC who could expect R0 resection. We analyzed the prognostic factors for overall survival among patients who underwent conversion surgery. Results: Overall, 638 patients with advanced pancreatic cancer were enrolled in this study. According to resectability, resectable cancer (R) was present in 180 patients, borderline resectable cancer (BR) was present in 60 patients, unresectable locally advanced cancer (UR-LA) was present in 252 patients, and unresectable cancer with distant metastasis (UR-M) was present in 146 patients. Conversion surgery was performed in 20 of the 398 UR cases (5.1%). The median period between the initial therapy and conversion surgery was 15.5 months. According to the Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, the treatment response was CR in one patient, PR in 13, SD in five, and PD in one. Downstaging was pathologically determined in all cases. According to the Evans grading system, grade I was observed in four patients (20%), grade IIb was observed in seven (35%), III was observed in seven (35%), and IV was observed in two (10%). We compared the overall survival period from initial treatment among patients undergoing conversion surgery; the median overall survival durations in the conversion surgery, R, BR, UR-LA, and UR-M groups were 73.7, 32.7, 22.7, 15.7, and 8.8 months, respectively. Multivariate analysis revealed that the presence or absence of chemoradiotherapy (CRT) and the RECIST partial response (PR)/complete response (CR) for the main tumor were statistically significant prognostic factors for overall survival among patients undergoing conversion surgery (p = 0.004 and 0.03, respectively). Conclusion: In UR-PDAC, it is important to perform multidisciplinary treatment, including CRT with conversion surgery.

Prognostic impact of serum cytokeratin 19 fragments in patient with metastatic urothelial cancer (mUC) treated with first-line chemotherapy.

473 Background: Even today, when several immune checkpoint Inhibitors have been approved for the treatment of metastatic urothelial cancer (mUC), cytotoxic chemotherapy (CTC) still remains the mainstay for first-line treatment. We believe that the prognostic factors for the first-line CTC have become more important again and need to be re-analyzed. Current guidelines do not yet provide recommendations for any serum tumor markers in patients with mUC. Previous studies have shown that serum cytokeratin 19 fragments levels (sCK) were correlated with depth of tumor invasion and metastatic burden in patients with bladder cancer. In this study we evaluated whether sCK, and other clinical parameters could predict overall survival (OS) in patients with mUC treated with CTC. Methods: Two hundreds fifty two patients with mUC received CTC from December 2006 to 2016 at our institution. sCK had been measured in 128 patients at diagnosis of mUC. OS rate were analyzed by Kaplan–Meier curves and log–rank test. Multivariate analysis was carried out using the Cox hazards model. Tumor burden (TB) was measured based on Response Evaluation Criteria In Solid Tumor (version 1.1). Results: Of 128 patients, with median age of 72 (44-93), 36 (28%) had lung metastasis, 11 (9%) had bone metastasis, 10 (8%) had liver metastasis (LM). Ninety five (74%) patients received platinum based chemotherapy as a first-line treatment. During the median follow-up period of 19 (1-89) months, 72 patients (70%) had died. A 1-year (1y) OS was 51% and a 2y-OS was 36%. On univariate analysis, performance status (PS) (HR2.0, p&lt;0.005), sCK (HR3.9, p&lt;0.001), CRP (HR4.0, p&lt;0.001), neutrophil-lymphocyte ratio (HR1.9, p&lt;0.049), LM (HR2.0, p=0.042) and TB (HR2.4, p&lt;0.001) were the significant prognostic factors for OS. On multivariate analysis, PS (HR2.0, 95%CI (1.05-3.85) p=0.036 ), sCK (HR3.1, 95%CI (1.3-8.3), p=0.011), and LM (HR3.0, 95%CI (1.06-6.98), p=0.022) were the independent prognostic factors for OS. Based on these 3 factors we divided patients into three groups, good risk (G, 0 factor), intermediate risk (I, 1 factor) and poor risk (P, 2-3 factors). There was a significant difference between the three groups. (G vs I: p&lt;0.001, I vs P: p=0.001). Conclusions: PS, sCK, and LM were the independent prognostic factors for OS in patients with mUC receiving CTC. For the patients in good or intermediate risk with this score, early exposure of ICIs should be performed after CTCs. Treatment strategy should be changed in patients with poor risk since CTC is primary refractory in such population.

Development and validation of circulating tumor cell (Epic Sciences) enumeration as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

157 Background: We evaluated the prognostic significance of circulating tumor cell (CTC) number as determined on the Epic Sciences platform in men with metastatic castration resistant prostate cancer (mCRPC) treated with an androgen receptor signaling inhibitor (ARSI). Methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a 1st, 2nd or 3rd line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N=175) or as a 1st and 2nd line therapy as part of the multi-center PROPHECY trial (NCT02269982) (Validation cohort, N=107). Enumeration was performed on the Epic Sciences platform and associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. Matched blood samples from the Validation cohort were to CTC counts measured on the CellSearch Circulating Tumor Cell kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (&lt; 3 CTCs/mL versus ≥ 3 CTCs/mL; HR = 1.8, (1.3-3.0, 95% CI)) and as a continuous variable when adjusting for line of therapy, presence of visceral metastases, PSA, lactate-dehydrogenase, and alkaline-phosphatase. The findings were validated in an independent dataset (PROPHECY trial) - (HR (95% CI) = 1.8, (1.1-3.0) for OS and 1.7 (1.1-2.9), for PFS). A strong correlation was observed between CTC counts determined in matched samples on the CellSearch and Epic platforms (r = 0.84). Conclusions: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.

Analysis of clinical outcomes and prognostic factors in patients treated with definitive chemoradiotherapy for oesophageal squamous cell carcinoma.

As patients receiving definitive chemoradiotherapy (dCRT) for oesophageal squamous cell carcinoma (ESCC) are heterogeneous, we aimed to identify prognostic factors and failure patterns after dCRT. From 2006 to 2015, 327 patients who received dCRT for ESCC were reviewed. Treatment response to dCRT was evaluated based on EORTC‐PET criteria with endoscopy and CT results. After dCRT, 296 patients (90.5%) achieved disease stabilisation, with 132 cases of complete response (CR) (40.4%), 158 of partial response (PR) (48.3%) and 6 of stable disease (SD) (1.8%); 31 patients (9.5%) had progressive disease (PD). Median overall survival (OS) from response evaluation was 24.0 months in the overall population. Post‐treatment clinical response was the most significant prognostic factor for OS in the multivariate analysis (median OS, 65.0 months for CR, 17.3 months for PR, 4.4 months for SD and 4.0 months for PD; p < 0.0001). Median progression‐free survival (PFS) in 296 patients who achieved disease stabilisation was 13.1 months, and only clinical response was a significant factor in the multivariate analysis. The median PFS of CR, PR and SD patients were 36.9, 9.2 and 2.8 months, respectively (p < 0.0001). The clinical response was also significantly associated with the predominant failure pattern (locoregional failure [81.6%] in the initial non‐PD group vs. distant metastasis [87.1%] in the initial PD group [p < 0.0001]). In conclusion, definitive chemoradiotherapy‐treated ESCC patients showed highly different prognoses after treatment especially according to the clinical response to chemoradiotherapy.

The treatment landscape of advanced angiosarcoma in Asia-A multi-national collaboration from the Asian Sarcoma Consortium.

Angiosarcoma (AS) is a rare disease with a dismal prognosis. The treatment landscape and prognostic factors for advanced AS, including locally advanced, unresectable, and metastatic disease remain elusive. The Asian Sarcoma Consortium is an international collaborative effort to understand the sarcoma treatment landscape in Asia. We undertook a retrospective chart review of AS patients seen in 8 sarcoma academic centers across Asia. Patients with complete clinical, treatment, and follow‐up data were enrolled. Overall, 276 advanced AS patients were included into this study; 84 (30%) of the patients had metachronous metastatic AS. The median age was 67 y; primary sites of AS was cutaneous in 55% and visceral in 45% of patients. In total, 143 (52%) patients received at least 1 line of systemic chemotherapy. The most common first‐line chemotherapy regimen used was paclitaxel (47.6%) followed by liposomal doxorubicin (19.6%). The median overall survival (OS) was 7.8 mo. Significant prognostic factors for OS included age > 65 (hazard ratio (HR) 1.54, P = .006), male gender (HR 1.39, P = .02), and a cutaneous primary AS site (HR 0.63, P = .004). The median progression‐free survival (PFS) for first‐line chemotherapy was 3.4 mo. PFS for single vs combination or paclitaxel vs liposomal doxorubicin chemotherapy regimens were comparable. This study provides an insight into the treatment patterns and prognostic factors of advanced AS patients in Asia. Prognosis of advanced AS remains poor. Data from this study serve as a benchmark for future clinical study design.

Do Red Blood Cell Transfusions Influence Long-Term Outcomes in Patients Undergoing Primary Surgery for Oral Squamous Cell Carcinoma?

There is no consensus on the impact of red blood cell (RBC) transfusion on patients with oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the association between RBC transfusions and overall survival (OS) and tumor-free survival (TFS) after operative treatment of OSCC. In this retrospective cohort study, all patients treated with primary surgery between 2003 and 2017 because of OSCC were chart reviewed. The occurrence and amount of RBC transfusions (0; 1-3; >3 units) was correlated with OS and TFS by Kaplan-Meier survival and Cox regression analyses. Demographic, clinical, and pathological parameters were also evaluated in order to identify confounding factors. Of 420 patients (243 [57.9%] male) with a mean age of 62.6years, 67 (16.0%) received RBC transfusion. There were statistically significant (P<.01) differences in 5-year OS respectively TFS in transfused patients for the Kaplan-Meier survival analysis (0 units=70.6%; [95% confidence interval {CI}: 65.0-75.4%] respectively 63.2% [95% CI: 57.4-68.4%], 1-3 units=47.2% [95% CI: 29.4-63.1%] respectively 40.6% [95% CI: 24.6-55.95%] and >3 units=48.9% [95% CI: 20.9-72.1%] respectively 30.5% [95% CI: 8.9-55.8%]). After multivariate adjustments for demographic, clinical, and pathological parameters, RBC transfusion could not be sustained as a significant prognostic factor in OS respectively TFS (1-3 units: hazard ratio=1.5 [95% CI: 0.7-3.2] respectively 1.3 [95% CI: 0.7-2.6]; >3 units: hazard ratio=1.2 [95% CI: 0.5 - 3.0] respectively 1.1 [95% CI: 0.5-2.4]). Although RBC transfusion was not identified as a significant prognostic parameter in multivariate analysis, a clear trend for shorter OS and TFS for transfused patients in univariate and Kaplan-Meier survival analysis could be shown.

Adjuvant radiotherapy and chemotherapy offer a recurrence and survival benefit in patients with resected perihilar cholangiocarcinoma

The objective of this study was to investigate the benefits of adjuvant treatment for patients with resected perihilar cholangiocarcinoma (PHC). Between 2001 and 2017, 196 patients with PHC adenocarcinoma underwent curative resection. The patients were divided into four groups according to adjuvant treatment type: surgery alone (S; N = 90), surgery with chemotherapy (S+CTx; N = 67), surgery with radiotherapy (S+RTx; N = 18), and surgery with chemoradiotherapy (S+ CRTx; N = 21). The median follow-up duration of the surviving patients was 58months. The 5-year rate of overall survival (OS) was 32%. In multivariate analysis, receiving S+CTx and S+CRTx were significant prognostic factors for OS. In subgroup analyses of the R1 resection patients, the S+CRTx group showed better OS than the S group (p < 0.05). In subgroup analyses of the stage III-IVA patients with a negative resection margin, the S+CTx and S+CRTx groups showed superior OS than the S group (p < 0.05). Our data suggest that adjuvant chemoradiotherapy might be considered for PHC patients with R1 resection. Adjuvant chemotherapy or chemoradiotherapy is suggested for stage III-IVA patients with R0 resection. The results of this study require validation through further prospective studies.

Evaluation of Prognostic Factors that Affect Survival Outcomes of Breast Cancer Patients with Brain Metastases: A Single Institutional Experience.

This study aimed to evaluate various prognostic factors that play a vital role in stratifying and guiding tailored treatment strategies and survival outcome in breast cancer patients with brain metastases (BM). Data regarding demography, clinical presentation, molecular subtypes, risk-stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event (survival) outcomes were analyzed by Kaplan-Meir method and compared using log-rank test. Univariate and multivariate analysis of relevant prognostic factors were performed and p-values ≤0.05 were considered statistically significant. A total of 88 patients (median age: 50 years) were included for this study. The median follow-up time of all surviving patients was ~20 months. During the follow-up, 82 (93.1%) patients died. The median survival of all patients was 12 months, with 1-year and 2-year overall survival (OS) rate of 51% and 22%, respectively. Based on univariate analysis, statistically significant prognostic factors for OS were molecular subtypes, number of BM, and Karnofsky Performance Status (KPS); however, number of BM and KPS emerged as independent predictors of survival based on multivariate analysis. We conclude that, there are other important prognostic factor, such as number of BM, which may affect the OS of these patients, in addition to variables included in the diagnosis-specific graded prognostic assessment score. Prospective studies evaluating these factors are necessary to further refine the stratification of patients, which will aid the initiation of appropriate treatment to improve the OS of patients.

The prognostic significance of intratumoral heterogeneity of 18F-FDG uptake in patients with oral cavity squamous cell carcinoma

Abstract Purpose This study aimed to evaluate the prognostic significance of two major indices of intratumoral heterogeneity of 18F-fluorodeoxyglucose uptake by positron emission tomography (PET)/computed tomography (CT), namely heterogeneity index (HI) and heterogeneity factor (HF), in patients with oral squamous cell carcinoma. Methods We performed a retrospective analysis of 62 patients who underwent resective surgery. HI, HF, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from pretreatment PET. HI was obtained by dividing SUVmax by SUVmean for the primary lesion; HF was obtained by taking the derivative (dV/dT) of the volume-threshold function from 30 to 70%. Univariate and multivariate analyses for the overall survival (OS) and disease-free survival (DFS) were performed using PET and clinicopathological parameters. Results Univariate and multivariate analyses of OS revealed that higher HI levels (threshold for the SUVmean is 30% of the SUVmax) were associated with poorer OS [hazard ratio (HR) = 11.57; 95% confidence interval (CI) = 1.45–92.28; P = 0.021]. Moreover, univariate and multivariate analyses of DFS revealed that higher TLG levels (threshold for the MTV and SUVmean is 4.0 of the SUV) were associated with poorer DFS (HR = 14.48; 95% CI = 1.27–164.78; P = 0.031). Conclusions HI and TLG may be statistically significant prognostic factors for OS and DFS, respectively.

A nomogram to predict the prognosis of patients with unresected rectal adenocarcinoma undergoing chemoradiotherapy: a population-based study.

Background: Chemotherapy combined with radiotherapy is the main treatment strategy for unresectable rectal cancer. However, the prognostic factors of patients with unresectable rectal cancer treated with radiotherapy and chemotherapy have not been systematically studied. Therefore, this study investigated the prognostic factors and prognosis based on surveillance, epidemiology and final results of the SEER medical insurance database.Methods: Primary rectum patients were selected from the SEER database. The independent prognostic factors associated with overall survival (OS), cancer-specific survival (CSS) and noncancer-related death were evaluated using the Kaplan-Meier method and log-rank test, a competing risk model, and the Cox proportional hazards regression model. Two nomograms were established for predicting the 1- and 3-year OS and CSS of patients.Results: A total of 3,998 rectal adenocarcinoma cancer patients who received chemoradiotherapy but had not undergone surgery were included in this study and divided into training (n = 3559) and validation cohorts (n = 439). Patients in the training cohort had a 1-year OS rate of 65.7±0.8%, a 3-year OS rate of 26.6±0.8%, a 5-year OS rate of 1.6±0.8%, and a median survival rate of 20.0 months (range, 19.22-20.8 months). The following factors were significant prognostic factors of OS: age (p< 0.001); tumour grade (p< 0.001); T stage (p< 0.001); M stage (p< 0.001); bone metastasis (p<0.001); brain metastases (p<0.001); liver metastases (p<0.001); lung metastases (p<0.001); marital status (p<0.001) and insurance status (p=0.005). Age (p< 0.001), tumour grade (p< 0.001), T stage (p< 0.001), M stage (p< 0.001), bone metastasis (p<0.001), brain metastases (p<0.001), liver metastases (p<0.001), lung metastases (p<0.001) and race (p=0.034) were independent prognostic factors of CSS. Age (p< 0.001), T stage (p< 0.001), N stage (p=0.007), M stage (p<0.001), liver metastases (p<0.001), lung metastases (p<0.001), marital status (p<0.001) and insurance status (p=0.019) were independently associated with noncancer-related death.Conclusion: Age, tumour grade, T and M stage, bone, brain, liver and lung metastases, marital status and insurance status are independent risk factors for the OS of rectal adenocarcinoma patients who have undergone chemoradiotherapy but have not undergone surgery. Age, tumour grade, T stage, M stage, bone, brain, liver, lung metastases and race were independent prognostic factors of CSS. Age, T, N and M stage, liver and lung metastases, marital status and insurance status, were independently associated with noncancer-related death. Interestingly, the earlier the T stage was, the higher the rate of noncancer-related death. Two nomograms were developed to predict OS and CSS, and the C-indexes were 0.6776 and 0.6744, respectively. Rectal cancer screening is strongly recommended for patients under the age of 50.

Long-term outcomes of cervical cancer patients with complete metabolic response after definitive chemoradiotherapy.

ObjectiveWe investigated the importance of metabolic parameters measured with 18F-fluorodeoxyglucose positron-emission tomography integrated with computed tomography (FDG-PET/CT) for predicting progression-free survival (PFS) and overall survival (OS) in cervical cancer with complete metabolic response (CMR) after chemoradiotherapy (ChRT).MethodsThe clinical data and PET parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 122 patients having CMR in post-treatment 18F-FDG-PET/CT delivered a median of 3.9 months after ChRT completion were analyzed.ResultsWith a median follow-up of 8.4 years, 55 patients (45%) presented with disease a median of 19.7 months after ChRT. For SUVp, MTVp, TLGp, SUVln, MTVln, and TLGp, the cut-off values for OS determined by receiver operating curve analysis were 15.8, 48.7 cm3, 552.3, 8.7, 7.0 cm3, respectively. All metabolic PET parameters were significant prognostic factors for OS and PFS in univariate analysis. International Federation of Gynecology and Obstetrics (FIGO) stage was predictive of both OS and PFS, while pelvic and/or para-aortic lymph node metastasis were predictive of OS only. In multivariate analysis, FIGO stage ≥IIB, MTVp ≥49.8 cm3, and TLGp ≥597.4 were predictive of worse OS. Advanced stage, presence of lymph node metastasis, higher TLGp, and larger MTVln were significant factors for poor PFS rates.ConclusionWe found that advanced stage and higher TLGp values were significant predictors for poor survival and higher progression rates. Volumetric PET parameters could be used to predict treatment outcomes in patients with CMR after definitive ChRT.

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

Background/Aim: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). Methods: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. Results: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). Conclusion: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.

Sarcopenia as a Predictor of Prognosis in Early Stage Ovarian Cancer.

BackgroundTo identify sarcopenia as a predictive prognostic factor of ovarian cancer in terms of survival outcome in patients with early-stage ovarian cancer.MethodsData of Konkuk University Medical Center from March 2002 to December 2017 were reviewed retrospectively. Eighty-two patients who underwent surgery due to early-stage (International Federation of Gynecology and Obstetrics stage I/II) ovarian cancer and had computed tomography (CT) images taken at the initial diagnosis were included. The initial CT scan images were analyzed with SliceOmatic software (TomoVision). A sarcopenia cutoff value was defined as a skeletal muscle index of ≤ 38.7 cm2/m2. Overall survival (OS) times were compared according to the existence of sarcopenia, and subgroup analyses were performed.ResultsA Kaplan-Meier analysis showed a significant survival disadvantage for patients with early-stage ovarian cancer when they had sarcopenia (P < 0.001; log-rank test). Sarcopenia remained a significant prognostic factor for OS in early-stage ovarian cancer, in a Cox proportional hazards model regression analysis (HR, 21.9; 95% CI, 2.0–199.9; P = 0.006).ConclusionThis study demonstrated that sarcopenia was predictive of OS in patients with early-stage ovarian cancer. Further prospective studies with a larger number of patients are warranted to determine the extent to which sarcopenia can be used as a prognostic factor in ovarian cancer.