Significant Prognostic Factors For Disease-specific Survival Research Articles

Long-Term Outcomes in a Phase II Study of Hypofractionated IGRT 60Gy/ 20F in Patients with Isolated Lymph Node Recurrence after Surgery for Esophageal Carcinoma

In oligo metastases in lymph node recurrence after surgery for esophageal cancer, since SBRT (BED>100 Gy10) to mediastinal and abdominal lymph node lesions was not an option due to toxicities in the organs at risk (OAR) such as vessels and gastrointestinal tract, we performed a prospective cohort study of hypofractionated IGRT for isolated lesions. The primary end-points of this study are disease specific survival (DSS) and late treatment toxicities. From 2011 to 2021, 60 Gy/20F/4-4.5wks (78 Gy10) hypofractionated IGRT was performed in a total ITT population of 70 patients after radical surgery (67 cases) and ESD (3 cases), who were diagnosed by CT/PET-CT as having solitary lymph node recurrence (62 cases) or up to 2 adjacent nodes (8 cases). The mean time from surgery to recurrence was 17.9 months (SD 18.1) with a mean age of 67.5 years (SD 9.3), and male to female ratio was 62:8. Pathological results showed that 63 patients (90%) had squamous cell carcinoma. The mean maximum diameter of lesions was 2.5 cm (SD; 1.1 cm). And 51 cases (73%) were treated with CRT concurrently using 5FU plus CDDP (FP), and the rest were treated with RT alone. Lymph node location was lower neck or upper mediastinum in 42 cases, middle and lower mediastinum in 16 cases, and abdomen in 12 cases, respectively. Treatment planning was performed by taking 4DCT fusing PET or MRI images. The Kaplan-Meier method and the Cox proportional hazards regression model were used for overall survival (OS), DSS, and progression free survival (PFS). The mean observation period was 38 months. Primary efficacy was CR in 45 cases (64%), but CR was maintained only in 29 cases (41%). Twenty-two of the 70 patients were relapse-free. OS were 53% and 34% at 2 and 5 years, DSS were 56% and 38% at 2 and 5 years, and PFS were 40% and 39% at 2 and 5 years, respectively. The site of first recurrence was the same or adjacent lymph nodes in 33 cases (47%) and distant metastases in 9 cases (13%). Number of tumors (1 vs. 2), age, and CRT were not significant prognostic factors for OS, DSS, or PFS. In a multivariate analysis, the time from surgery to recurrence ≥12 months was the only significant prognostic factor for PFS (p = 0.018, HR0.50). The same multivariate analysis showed that the only significant prognostic factor for DSS was the location of the recurrent lymph node in the neck and upper mediastinal regions (p = 0.009, HR 0.59). The only late adverse events of Grade 2 or higher were Grade 2 pleural effusion (little and transient) in 6 cases and Grade 2 radiation pneumonitis in 1 case. No acute adverse events were observed other than hematologic toxicity due to FP administration. In locally advanced esophageal cancer, a relatively reliable regional lymph node dissection is often performed, so there is still a chance to aim for cure in cases of solitary recurrence. We found that if the lesion is solitary, localized RT of about 60 Gy/20F/4-4.5 weeks with IGRT can achieve a long-term survival in 40% of patients without any significant adverse events.

Surgical management of carcinomas of the infratemporal fossa and skull base: patterns of failure and predictors of long-term outcomes.

Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma. All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors' institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes. Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence. The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.

Prevalence of human papillomavirus and implication on survival in Chinese penile cancer.

We assessed the prevalence of HPV DNA in a large series of Chinese penile cancer and examine its association with the histological subtype, p16INK4a expression, and prognosis. We pathologically categorized 226 invasive penile squamous cell carcinomas and assessed HPV genotyping by real-time PCR and p16INK4a immunohistochemistry. The results were correlated with histopathological and clinical parameters and disease-specific survival (DSS). HPV DNA was detected in 32.7% (74/226) of penile cancer cases. The most frequent genotype was HPV 16 (64/74, 86.5%), followed by HPV 18 (6/74, 8.1%). Fifty-nine (26.1%) cases were positive for the p16INK4a expression, and p16INK4a expression had a sensitivity of 56.8% (95% CI, 45.2-68.3%) and a specificity of 88.8% (95% CI, 83.8-93.9%) for defining HPV status. HPV DNA (P = 0.019), p16INK4a (P = 0.038), age (P = 0.018), grade of differentiation (P = 0.001), lymph nodes (P < 0.001), T stage (P < 0.001), M stage (P < 0.001), and lymphovascular invasion (LVI, P = 0.001) were prognostic factors for DSS. HPV-positivity (HR 0.334; 95% CI, 0.158-0.705, P = 0.004) was still a significant prognostic factor for DSS in the multivariate Cox regression model. HPV DNA was observed in one third of Chinese penile carcinoma cases. The p16INK4a expression can indicate high-risk human papillomavirus (HR-HPV). HPV-positive penile tumors confer a survival benefit over HPV-negative tumors.

Prognostic Role Of Computed Tomography Textural Features In Early-Stage Non-Small Cell Lung Cancer Patients Receiving Stereotactic Body Radiotherapy.

PurposeThe imaging features of patients with early-stage non-small cell lung cancer (NSCLC) receiving stereotactic body radiotherapy (SBRT) are crucial for the decision-making process to establish a treatment plan. The purpose of this study was to predict the clinical outcomes of SBRT from the textural features of pretreatment computed tomography (CT) images.Patients and methodsForty-one early-stage NSCLC patients who received SBRT were included in this retrospective study. In total, 72 textural features were extracted from the pretreatment contrast-enhanced CT images. Survival analysis was used to identify high-risk groups for progression-free survival (PFS) and disease-specific survival (DSS). Receiver operating characteristic (ROC) curve analysis was utilized to estimate the diagnostic abilities of the textural parameters. Univariable and multivariable Cox regression analyses were performed to evaluate the predictors of PFS and DSS.ResultsFour parameters, including entropy (P=0.003), second angular moment (SAM) (P=0.04), high-intensity long-run emphasis (HILRE) (P=0.046) and long-run emphasis (LRE) (P=0.042), were significant prognostic features for PFS. In addition, contrast (P=0.008), coarseness (P=0.017), low-intensity zone emphasis (LIZE) (P=0.01) and large number emphasis (LNE) (P=0.046) were significant prognostic factors for DSS. In the ROC analysis, the area under the curve (AUC) of coarseness for local recurrence (LR) was 0.722 (0.528–0.916), and the AUC of entropy for lymph node metastasis (LNM) was 0.771 (0.556–0.987). The four highest AUCs for distant metastasis (DM) were 0.885 (0.784–0.985) for LNE, 0.846 (0.733–0.959) for SAM, 0.731 (0.500–0.961) for LRE and 0.731 (0.585–0.876) for contrast. In the multivariable analysis, smoking and entropy were independent prognostic factors for PFS.ConclusionThis exploratory study reveals that textual features derived from pretreatment CT scans have prognostic value in early-stage NSCLC patients treated with SBRT.

Clinical Significance of Histological Effect and Intratumor Stromal Expression of Tenascin-C in Resected Specimens After Chemoradiotherapy for Initially Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma.

Tenascin-C (TN-C) is an extracellular matrix protein that is up-regulated in pancreatic ductal adenocarcinoma (PDAC) stroma and associated with tumor invasion. We examined intratumor stromal expression of TN-C in resected specimens and the histologic effect of chemoradiotherapy (CRT) as prognostic indicators in initially locally advanced unresectable (UR-LA) PDAC. Among 110 UR-LA PDAC patients enrolled in the CRT protocol from February 2005 to December 2015, 46 who underwent curative-intent resection were classified as high (tumor destruction >50%) and low (≤50%) responders according to the Evans grading system. Tenascin-C expression was immunohistologically evaluated in all patients except one with complete response. The 12 high responders achieved a significantly higher R0 rate than did the 34 low responders (83.3 vs 47.1%), but disease-specific survival (DSS) time was not significantly different (median survival time, 29.8 vs 21.0 months). Tenascin-C expression was inversely correlated with histologic effect of CRT. The 22 patients with negative TN-C had significantly longer DSS time than did the 23 with positive TN-C (29.3 vs 17.1 months). In multivariate analysis, only TN-C expression was a significant prognostic factor for DSS. Intratumor stromal expression of TN-C is a strong prognostic indicator in UR-LA PDAC patients with resection after CRT.

Acral lentiginous melanoma: a skin cancer with unfavourable prognostic features. A study of the German central malignant melanoma registry (CMMR) in 2050 patients.

Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors associated with ALM have only been verified in small-sized cohorts because of the low incidence of ALM worldwide. To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society. The Kaplan-Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease-specific survival (DSS) curves, which were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS. In total, 2050 patients with ALM were identified from 58949 patients with CM recorded by the CMMR with follow-up data. In multivariate analyses, age (P=0·006), ulceration (P=0·013), tumour thickness (P<0·001) and tumour spread (P<0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors. ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.

A Validated Prognostic Biomarker Score for Adult Patients with Nonmetastatic Soft Tissue Sarcomas of the Trunk and Extremities

BACKGROUND: The prognostic value of serum biomarkers in soft tissue sarcoma (STS) is limited, and its clinical applicability is compromised by a common inability to adjust for important confounders. The aim of this study was to determine the prognostic value of pretreatment biomarkers on disease-specific survival (DSS) adjusted for confounders. METHODS: The study included 818 patients with localized STS. Pretreatment levels of albumin, C-reactive protein, hemoglobin, neutrophils, and lymphocytes were tested individually and combined in prognostic scores: neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), and Aarhus Composite Biomarker Score (ACBS) which includes all five biomarkers. Patients were randomly split into a test cohort and a validation cohort. The prognostic value of biomarkers on DSS was estimated using crude and adjusted Cox proportional hazard models. The different biomarker scores were compared using Akaike's information criteria. RESULTS: In the test cohort of 403 patients, all biomarkers except lymphocyte count were significant prognostic factors for DSS also after adjusting for confounders. NLR, GPS, and ACBS were independently associated with decreased survival; however, ACBS was significantly superior to NLR (P=.02) and GPS (P=.002). These findings were validated in the randomly assigned validation cohort of 415 patients. In the pooled data of 818 patients, the ACBS performed better than GPS and NLR. ACBS 2 was independently associated with decreased DSS compared to ACBS 0, hazard ratio 2.3[95% confidence interval: 1.5-3.5], P<.001. CONCLUSION: Patients with abnormal values in more than one serum biomarkers had a significant additional risk of dying compared to patients with only one abnormal value. ACBS was validated as an independent prognostic factor that is superior to both NLR and GPS.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the hypopharynx treated with concurrent chemoradiotherapy

The purpose of the study is to review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma(SCC) of the hypopharynx and to evaluate the factors affecting survival and larynx preservation. Retrospective study. T he records of 102 patients with Stage III or IV resectable SCC of the hypopharynx treated with CCRT between January 1998 and August 2010 were reviewed. Of the 102 patients, 62 were treated with high dose regimens including cisplatin, 5-fluorouracil, methotrexate, leucovorin or docetaxel, cisplatin, and 5-fluorouracil. The remaining 40 were treated with low-dose regimens including carboplatin and uracil-tegafur, weekly docetaxel, or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8–2.0 Gray (Gy), to a total dose of 64.8–70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan–Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for OS, DSS, and DSS with larynx preservation. The 5-year OS and DSS for all patients treated with CCRT were 51.3 and 64.3 %, respectively. The 5-year DSS with larynx preservation was 55.5 %. On multivariate analysis, the content of chemotherapy was a significant predictor of OS and DSS for patients undergoing CCRT ; N stage was a significant prognostic factor for DSS and larynx preservation. T he treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the N stages of SCC of the hypopharynx.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the larynx treated with concurrent chemoradiotherapy

To review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and to evaluate the factors affecting survival and larynx preservation. Retrospective study. The records of 102 patients with stage III or IV resectable SCC of the larynx treated with CCRT between February 1994 and March 2009 were reviewed. Of 102 patients, 59 were treated with high-dose regimens, including cisplatin, 5-fluorouracil (5-FU), methotrexate, and leucovorin or docetaxel, cisplatin, and 5-FU, and 43 were treated with low-dose regimens, including carboplatin and uracil-tegafur or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8–2.0 Gray (Gy), to a total dose of 66.0–70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan–Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for DSS and DSS with larynx preservation. The 5-year OS and DSS for all patients treated with CCRT were 63.9 and 70.7 %, respectively. The 5-year DSS with larynx preservation was 54.1 %. On multivariate analysis, N stage, synchronous multiple primary cancers, and the contents of chemotherapy were significant predictors of OS for patients undergoing CCRT; T stage, N stage, and the contents of chemotherapy were significant prognostic factors for larynx preservation. The treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the T and N stages of laryngeal SCC. It is important to diagnose multiple synchronous primary cancers before CCRT.

Impact of the Epstein–Barr virus positivity on Hodgkin's lymphoma in a large cohort from a single institute in Korea

Epstein-Barr virus (EBV) is considered a prognostic marker in Hodgkin lymphoma (HL) patients, but previous studies have yielded mixed findings because of the confounding effects of factors including age. We examined the prognostic impact of EBV status on 159 patients with HL. The median age at diagnosis was 32 years (range, 4-77 years). The median follow-up time was 5.83 years (range, 0.33-19.69 years). Tumor cell EBV status was positive in 34.5 %. EBV-positive HL was associated with age of ≥ 25 years, male gender, B symptoms, advanced stage, high-risk IPS, nonnodular sclerosis subtype, and treatment with chemotherapy only (P < 0.05). The 5-year disease-specific survival (DSS) rates were 94.1 and 76.4 % for the EBV-negative and EBV-positive HL, respectively, (P < 0.001). On univariate analysis, event-free survival, DSS, and overall survival (OS) were significantly associated with age 40 years or older, B symptoms, and high-risk international prognostic score (≥ 4). On multivariate analysis, EBV positivity was found to be a significant prognostic factor for DSS, particularly in adults 25 years or older. Subgroup analysis showed significant association of EBV-positive HL with poorer DSS and OS in adults 25 years or older with advanced stage disease. In the present series of HL patients, the presence of EBV in tumor cells is associated with adverse prognostic factors. EBV-positive HL is significantly associated with poorer DSS in all age groups.

Risk stratification of survival by lymphovascular invasion, pathological stage, and surgical margin in patients with bladder cancer treated with radical cystectomy

The aim of this study was to investigate prognostic factors and develop a prognostic factor-based risk stratification model for disease-specific survival (DSS) in a radical cystectomy (RC) series. The patient cohort comprised 194 consecutive patients with bladder cancer treated with RC. Univariate and multivariate Cox proportional hazard model analyses were performed to identify significant prognostic factors for DSS. A risk stratification model was developed based on the relative risks (RRs) of DSS. Median follow-up period was 26.8 months. The 1-, 3-, and 5-year DSS were 88.0, 74.0, and 64.9%, respectively. In the univariate analysis, pathological T (pT) (≥ pT2), lymphovascular invasion (LVI), non-urothelial carcinoma component, surgical margin (SM), and lymph node metastases (pN) were significantly associated with poor prognosis. In the multivariate analysis, pT (≥ pT2), LVI, and SM were independent factors for predicting poor prognosis. Based on these results, patients were stratified into three risk groups: low (RR = 1.00-3.626), intermediate (5.860-9.826), and high (21.24). The 1-, 3-, and 5-year survival rates were 96.9, 85.1, and 85.1% in the low-risk group, 83.0, 63.4, and 43.8% in the intermediate group, and 51.0, 19.4, and 19.4% in the high-risk group, respectively. The differences among these groups were significant. In our RC series, pT (≥ pT2), LVI, and SM were independent prognostic factors. This information may be useful to identify patients with poor prognosis, who might be good candidates for innovative treatment.

Surgeon-related factors and outcome in rectal cancer.

To determine whether surgical subspecialty training in colorectal surgery or frequency of rectal cancer resection by the surgeon are independent prognostic factors for local recurrence (LR) and survival. Variation in patient outcome in rectal cancer has been shown among centers and among individual surgeons. However, the prognostic importance of surgeon-related factors is largely unknown. All patients undergoing potentially curative low anterior resection or abdominoperineal resection for primary adenocarcinoma of the rectum between 1983 and 1990 at the five Edmonton general hospitals were reviewed in a historic-prospective study design. Preoperative, intraoperative, pathologic, adjuvant therapy, and outcome variables were obtained. Outcomes of interest included LR and disease-specific survival (DSS). To determine survival rates and to control both confounding and interaction, multivariate analysis was performed using Cox proportional hazards regression. The study included 683 patients involving 52 surgeons, with > 5-year follow-up obtained on 663 (97%) patients. There were five colorectal-trained surgeons who performed 109 (16%) of the operations. Independent of surgeon training, 323 operations (47%) were done by surgeons performing < 21 rectal cancer resections over the study period. Multivariate analysis showed that the risk of LR was increased in patients of both noncolorectal trained surgeons (hazard ratio (HR) = 2.5, p = 0.001) and those of surgeons performing < 21 resections (HR = 1.8, p < 0.001). Stage (p < 0.001), use of adjuvant therapy (p = 0.002), rectal perforation or tumor spill (p < 0.001), and vascular/neural invasion (p = 0.002) also were significant prognostic factors for LR. Similarly, decreased disease-specific survival was found to be independently associated with noncolorectal-trained surgeons (HR = 1.5, p = 0.03) and surgeons performing < 21 resections (HR = 1.4, p = 0.005). Stage (p < 0.001), grade (p = 0.02), age (p = 0.02), rectal perforation or tumor spill (p < 0.001), and vascular or neural invasion (p < 0.001) were other significant prognostic factors for DSS. Outcome is improved with both colorectal surgical subspecialty training and a higher frequency of rectal cancer surgery. Therefore, the surgical treatment of rectal cancer patients should rely exclusively on surgeons with such training or surgeons with more experience.