Distant Failure-free Survival Research Articles

Vision Transformer-Based Multilabel Survival Prediction for Oropharynx Cancer After Radiation Therapy

A reliable and comprehensive cancer prognosis model for oropharyngeal cancer (OPC) could better assist in personalizing treatment. In this work, we developed a vision transformer-based (ViT-based) multilabel model with multimodal input to learn complementary information from available pretreatment data and predict multiple associated endpoints for radiation therapy for patients with OPC. A publicly available data set of 512 patients with OPC was used for both model training and evaluation. Planning computed tomography images, primary gross tumor volume masks, and 16 clinical variables representing patient demographics, diagnosis, and treatment were used as inputs. To extract deep image features with global attention, we used a ViT module. Clinical variables were concatenated with the learned image features and fed into fully connected layers to incorporate cross-modality features. To learn the mapping between the features and correlated survival outcomes, including overall survival, local failure-free survival, regional failure-free survival, and distant failure-free survival, we employed 4 multitask logistic regression layers. The proposed model was optimized by combining the multitask logistic regression negative-log likelihood losses of different prediction targets. We employed the C-index and area under the curve metrics to assess the performance of our model for time-to-event prediction and time-specific binary prediction, respectively. Our proposed model outperformed corresponding single-modality and single-label models on all prediction labels, achieving C-indices of 0.773, 0.765, 0.776, and 0.773 for overall survival, local failure-free survival, regional failure-free survival, and distant failure-free survival, respectively. The area under the curve values ranged between 0.799 and 0.844 for different tasks at different time points. Using the medians of predicted risks as the thresholds to identify high-risk and low-risk patient groups, we performed the log-rank test, the results of which showed significantly larger separations in different event-free survivals. We developed the first model capable of predicting multiple labels for OPC simultaneously. Our model demonstrated better prognostic ability for all the prediction targets compared with corresponding single-modality models and single-label models.

Post-Progression Survival in Patients with Oligometastatic or Polymetastatic Pancreatic Adenocarcinoma

Distant progression following surgical resection of stage I-III pancreatic ducal adenocarcinoma (PDAC) is a major cause of morbidity and mortality. Herein, we investigated the impact of tumor burden at the time of distant progression on survival. We hypothesize that patients with limited number of metastases (≤5) in a single organ will have improved survival post progression. We queried our institutional database for patients with the following inclusion criteria: 1-Stage I-III PDAC who underwent curative resection, and 2-Metachronous single organ (liver or lung) distant failure >3 months from the date of surgery. Patients with serosal and/or multiple organ metastases were excluded. Single organ metastases other than liver or lung were also excluded. Patients were stratified into oligometastatic (≤5 tumors), and polymetastatic (>5 tumors). Primary endpoint was survival post failure, while secondary endpoints were distant failure free survival (DFFS) and overall survival. Reverse KM curve was used to calculate median follow up. KM curves were plotted for DFFS identified from date of surgery until date of distant failure, survival post failure was identified from date of distant failure until death/last follow up, and overall survival was identified from date of surgical resection until death/last follow up. Out of 128 patients who developed metachronous distant progression following surgical resection, we identified 76 patients who met the inclusion criteria with a median follow up of 50 months. Among those, at the time of distant failure, 63% (n = 48) and 37% (n = 28) patients had ≤5 vs >5 metastases respectively. Median number of metastases was one (range 1-5) and eight (range 6-33), while 12 and 11 patients developed local failure in the oligometastatic and polymetastatic cohorts respectively. Among the 48 patients who developed oligometastases, 69% (n = 33) and 31% (n = 15) had liver and lung metastases respectively. On the other hand, 68% (n = 19) and 32% (n = 9) had liver and lung polymetastases respectively. Median DFFS was 11, and 9 months (HR = 1.59, 95 % CI 0.95-2.64, p value = 0.046), survival post distant failure was 17.8 and 5.3 months (HR = 3.03, 95 % CI 1.52-6.01, p value<0.0001), and median survival was 29.8, and 16.7 months (HR = 2.52, 95 % CI 1.31-4.86, p value = 0.0007) among patients with oligometastases and polymetastases respectively. Within the surgically resected stage I-III PDAC who developed single organ liver or lung metachronous disease, oligometastases (one-five lesions) were more prevalent, had more durable DFFS, had improved survival post failure, and a longer median survival compared to patients with polymetastatic recurrence (>five metastases). Trials on treatment of metastatic PDAC should stratify by number of metastases, and the oligometastatic subset may derive survival benefit from ablative radiation therapy.

Significance of neutrophil to lymphocyte ratio as a predictor of outcome in head and neck cancer treated with definitive chemoradiation.

The role of host immune system in carcinogenesis and response to treatment is increasingly studied, including predictive potential of circulating neutrophils and lymphocytes. The objective of the study was to evaluate the prognostic value of pre- and post-treatment neutrophil-to-lymphocyte (NLR) for treatment outcome in patients diagnosed with squamous cell carcinoma of head and neck (HNSCC) treated with definitive chemoradiation. Electronic medical records of patients were evaluated and NLR was calculated. Cox regression was used to assess the impact of selected variables on overall survival (OS), disease specific survival (DSS), progression free survival (PFS) and distant failure free survival (DFFS). Logistic regression was used to estimate odds ratios of complete response with NLR. 317 patients' records were included in the study. Increases in both pre-and post-NLR were associated with decreased OS in univariable analysis [hazard ratio (HR): 2.26 (1.25-4.07), p = 0.0068 and HR: 1.57 (1.03-2.37), p = 0.035 respectively). Post-NLR remained significant for OS in multivariable analysis [HR: 1.93 (1.22-3.1), p = 0.005] as well as for unfavorable DSS [HR: 2.31 (1.22-4.4), p = 0.01]. Pre-treatment NLR and nodal status correlated with shorter DFFS in multivariable analysis [HR 4.1 (1.14-14), p = 0.03 and HR 5.3: (1.62-18), p = 0.0062, respectively]. Strong correlation of increased both pre- and post-NLR with probability of clinical tumor response (CR) was found [odds ratio (OR): 0.23 (0.08-0.6), p = 0.003, and OR: 0.39 (0.2-0.8), p = 0.01 respectively]. NLR evaluated before and post treatment was a strong predictor of unfavorable treatment outcome and can be used for risk evaluation and clinical decision about treatment and post-treatment surveillance.

Pretreatment and Posttreatment Tumor Metabolic Activity Assessed by FDG-PET/CT as Predictors of Tumor Recurrence and Survival Outcomes in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n=163) and follow-up FDG-PET/CT at 3 or 6 months (n=71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P=.006), >12.3 for PFS (aHR, 2.80, P=.011), and >12.6 for OS (aHR, 3.00, P=.003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P=.018), and 53% at 6 months (aHR, 0.12, P=.046) were associated with improved local failure-free survival. Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.

A single center retrospective study assessing the prognostic significance of pre-treatment neutrophil/lymphocyte ratio in locally advanced nasopharyngeal carcinoma.

In light of the growing evidence suggesting the impact of inflammatory parameters on the survival of individuals with cancer, this research assessed the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in individuals diagnosed with locally advanced nasopharyngeal carcinoma (NPC) prior to undergoing intensity-modulated radiation therapy (IMRT). A total of 163 individuals diagnosed with locally advanced NPC treated with IMRT at our hospital between January 2012 and December 2017 were included in this research. For each patient, the absolute counts of neutrophils and lymphocytes were recorded, and the NLR was calculated at the first diagnosis. To determine the optimal cut-off values for NLR, receiver operating characteristic (ROC) curve analysis was conducted. The effects of the determined cut-off value on local failure-free survival (LFFS), overall survival (OS), progression-free survival (PFS), and distant failure-free survival (DFFS) were evaluated employing the Cox regression model. The median follow-up duration for the individuals in this study was 15 months (ranging from 6 to 79 months). According to the determined NLR cut-off value of 3.27, individuals were classified into two groups (high NLR and low NLR). Individuals in the high-NLR group had remarkably poorer 3-year OS (62.8% vs. 91.7%), PFS (51.4% vs. 82.4%), and DFFS (70.7% vs. 89.6%) compared to the low-NLR group. Furthermore, the outcomes of univariate and multivariate survival analyses revealed that NLR served as an independent predictor of DFFS (HR: 2.81, 95% CI: 1.195-6.608, P=0.018), OS (HR: 3.1, 95% CI: 1.211-7.935, P=0.018), and PFS (HR: 2.21, 95% CI: 1.133-4.292, P=0.02). Elevated NLR exhibited a significant correlation with reduced OS, DFFS, and PFS. These findings suggest that NLR holds promise as a cost-effective and reliable marker for the prediction of clinical outcomes among patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Furthermore, incorporating NLR into clinical decision-making regarding LANPC treatment strategies may contribute to a more targeted approach aimed at reducing the risk of distant failure.

Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis

BackgroundTo analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients.MethodsConsecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05.ResultsA total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 – 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3–4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%).ConclusionsOur classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

The effect of primary tumor volume on the prognosis of nasopharyngeal carcinoma in era of volumetric modulated arc therapy: a propensity score matched cohort study

ObjectiveThe role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. MethodsBetween January 20 and November 2011, 498 consecutive NPC patients with stage I–IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. ResultsThe 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTV ≤ 38 mL vs. PTV > 38 mL were 94.1% vs. 90.4% (p = 0.063), 87.9% vs. 76.3% (p < 0.001), 78.5% vs. 58.5% (p < 0.001) and 86.3% vs. 66.7% (p < 0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (p = 0.034), DFS (p = 0.002) and OS (p = 0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, p = 0.025. ConclusionsPTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTV > 38 mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. Level of evidenceIII.

Prognostic Factors for Survival in Patients With High-grade Chondrosarcoma

Chondrosarcoma (CS) is a rare primary malignant bone tumor, which is the second most common tumor after osteosarcoma. Since chemotherapy and radiotherapy have poor efficacy for CS, amputation or surgical wide resection is the main strategy for localized high-grade CS, making CS therapy difficult. As studies on high-grade CS are limited owing to its rare nature, there are many unknown prognostic factors for survival. This retrospective cohort study included 44 patients with high-grade CS who underwent surgery at a single institution. Overall survival (OS), distant failure-free survival (DFFS), and local failure-free survival (LFFS) were evaluated using the Kaplan-Meier method. Furthermore, we evaluated prognostic factors for survival in patients with high-grade CS using univariate and multivariate analyses. The 5-year OS, LFFS, and DFFS rates of high-grade CS were 75.9%, 90.8%, and 66.5%, respectively. Univariate analysis revealed that tumor size, tumor grade, and surgical margin were significant prognostic factors for OS and DFFS, and distant metastasis was significantly associated with OS. Furthermore, the multivariate analysis indicated that the presence of local recurrence and distant metastasis was significantly associated with OS. Local recurrence and distant metastasis were significant prognostic factors for high-grade CS.

Multi-Institutional Matched Comparison of Radical Cystectomy to Trimodality Therapy for Muscle Invasive Bladder Cancer (MIBC)

<h3>Purpose/Objective(s)</h3> Prior randomized controlled trials (RCT) comparing bladder preservation to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) closed early due to lack of accrual. Given that no future RCTs are foreseen, and in the absence of level 1 data, we aimed to provide the best evidence possible on outcomes of matched cohorts comparing trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to RC in order to guide management. <h3>Materials/Methods</h3> This retrospective analysis included 703 patients with MIBC clinical stage T2-T3/4aN0M0 MIBC urothelial carcinoma of the bladder, 421 RC and 282 TMT who would have been eligible for both TMT or RC, treated at three tertiary referral academic institutions between 2005-2017. To compare homogeneous cohorts, all patients included in this analysis had solitary tumors <7 cm, no or unilateral hydronephrosis, and no extensive carcinoma in situ. Treatment propensity scores were estimated using logistic regression, and patients were matched 3:1 with replacement. Covariates included age, sex, clinical T stage, hydronephrosis, (neo)adjuvant chemotherapy, body mass index, smoking history, and ECOG status. Overall survival (OS) was estimated with adjusted Cox models; cancer-specific survival (CSS), distant failure-free survival, pelvic nodal failure-free survival and metastasis-free survival (combined distant and pelvic nodal failure) were estimated with adjusted competing risk models. Our primary endpoint of interest was metastasis-free survival. The analysis was performed as intent-to-treat. <h3>Results</h3> The 3:1 matched cohort comprised of 1,116 patients (834 RC vs 282 TMT). After matching, age (71.3 vs 71.6), cT2 clinical stage (88 vs 90%), presence of hydronephrosis (12 vs 10%), and use of (neo)adjuvant chemotherapy (60 vs 65%) was similar between RC and TMT cohorts. Salvage cystectomy was performed in 38 patients (13%) treated by TMT. At 5 years, metastasis-free (73 vs 78%, p=0.07), distant failure-free (78 vs 82%, p=0.14), and pelvic nodal failure-free (96 vs 94%, p=0.33) survival were not statistically different between RC and TMT, whereas CSS and OS favored TMT (78 vs 85%, p=0.02; 66 vs 78%, p<0.001). Outcomes for RC and TMT were not different among centers. Final pT stage in the RC patients was: pT0 14%, pT1 7%, pT2 29%, pT3/4 42% and N+ 24%. Peri RC mortality was 2.1% and median number of nodes removed was 40. NMIBC recurrence occurred in 57/282 (20.2%) TMT patients. <h3>Conclusion</h3> This large multi-institutional contemporary study provides the best evidence to date, in the absence of randomized trials, supporting TMT for select patients with MIBC. Oncologic outcomes seem to be equivalent between TMT and RC, affirming the position that TMT should be offered as an effective alternative.

Delta Radiomic Signature from Neoadjuvant Pancreas Cancer Radiation Planning Volume is Superior to Tumor Proper Volume to Predict Surgical Failures

<h3>Purpose/Objective(s)</h3> Predicting outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who underwent surgical resection following neoadjuvant therapy is critical for decision making to optimize therapy. Delta radiomics may be a meaningful way to exploit changes in tumor features after preoperative therapy. Given the heterogeneity and infiltrative nature of the tumor, there is a lack of a standard methodology for identifying the tumor volume to be used for feature extraction. We hypothesize that a radiation planning volume inclusive of the tumor infiltrative regions is more predictive than a tumor proper volume that only includes the homogenous part of the tumor. <h3>Materials/Methods</h3> We reviewed our institutional database for patients with the following inclusion criteria: 1- histopathological diagnosis of PDAC, 2- received neoadjuvant chemotherapy and/or radiation therapy followed by surgical resection, and 3- have available CT scans before and after neoadjuvant therapy. We adopted two different methods to contour the tumor: A- "Tumor proper": including only the core mass component in the pancreas and immediately extending from the pancreas with homogeneous Hounsfield units, 2- "GTV": Including tumor proper in addition to the heterogonous infiltrating part of the tumor surrounding the pancreas, soft tissue and vessels if involved. We extracted 257 radiomic features from the segmented volumes and used the net changes between pre- and post-therapy as the delta-radiomic features. We built Cox Proportional Hazards models with a step forward feature selection method using each of the two volumes independently and C-index was used to assess the models. Outcomes were disease free and distant failure free survivals. <h3>Results</h3> Fifty-eight patients met the inclusion criteria. Thirty-five (60%) were of male gender with a median age of 67 years. Forty-eight patients (83%) presented with ECOG performance status of 0-1. Borderline and locally advanced tumors were reported in 25 patients (43%). All patients receive neoadjuvant chemotherapy, while 12 patients (21%) received neoadjuvant radiation therapy. FOLFIRNOX and gemcitabine/nab-paclitaxel were administered in 39 (67%) and 16 (28%) patients respectively. Pancreatoduodenectomy was done in 41 patients (71%). Following neoadjuvant therapy, median CA 19-9 dropped from 291 to 29 U/mL. For the disease-free survival, C-indices for the radiomic model were 0.662 (95% CI: 0.656, 0.668) and 0.736 (95% CI: 0.731, 0.741) for the Tumor proper and GTV respectively. For the distant failure free survival, the C-indices for the radiomic model were 0.677 (95% CI: 0.669, 0.684) and 0.729 (95% CI: 0.723, 0.736) for the Tumor proper and GTV respectively. <h3>Conclusion</h3> Inclusion of the infiltrative volumes consistently resulted in a more predictive delta radiomic model in all tested outcomes when compared to features extracted from the homogenous intrapancreatic part of the tumor only. External and prospective validation is needed to further investigate this finding.

Effects of Expansion Size from Gross Tumor Volume to Planning Target Volume on Control Rates and Patterns of Recurrence in Conventionally Fractionated Radiotherapy for WHO Grade I Meningiomas

<h3>Purpose/Objective(s)</h3> In single fraction stereotactic radiosurgery (SRS) for WHO grade I meningiomas, no- or minimal GTV to PTV margin is accepted practice with good outcomes. For complex tumors not eligible for SRS due to size or proximity to critical structures, there has been historical heterogeneity in target volume expansions practices, ranging from margins of a few mm to up to 2 cm. Additional margin is typically added for fractionated treatments to account for setup variability and less precise imaging and setup technique. Larger expansions result in treatment of uninvolved brain parenchyma and organs at risk, which is a concern in patients with expected long survivals. We sought to evaluate whether there is a control difference based on GTV to PTV expansion size in fractionated radiotherapy with either stereotactic or conventional conformal technique. <h3>Materials/Methods</h3> With IRB approval, we identified 87 patients from an institutional database with imaging-defined or WHO grade I meningioma treated with either 3D or IMRT radiation with 5 to 15 mm expansions from GTV (with or without intermediate CTV) or fractionated stereotactic radiotherapy (fSRT) using a system with ≤ 3mm GTV to PTV expansions, treated between 1999 and 2018 with at least 2 years of follow-up. All treatments were delivered using 1.8 Gray (Gy) fractions. Kaplan-Meier estimators were used for local failure-free survival (LFFS), marginal-failure free survival (MFFS) and distant failure-free survival (DFFS) analysis, with censoring occurring at failure event or most recent MRI. Local failure was defined as within the treatment field, marginal within 2 cm, and distant as beyond 2 cm. Patient clinical and demographic characteristics analyzed with χ² testing. <h3>Results</h3> With a median follow-up of 9.0 years, 25 patients (29%) received 3D or IMRT and 62 patients (71%) received fSRT. Doses delivered varied from 50.4-54 Gy, with the majority (71%) receiving 54 Gy. Thirty-two (37%) underwent surgery; 24 were sub-total resections. Total events were low, with 4 local failures (5%), 1 marginal failure (1%) and 1 distant failure (1%). The fSRT and 3D/IMRT groups each had two local failures; 3/4 local failures occurred in areas near critical organs at risk (two in suprasellar region, one in cavernous sinus). Extent of surgical resection was not correlated with risk for local failure. For 3D/IMRT vs fSRT, 5- and 10-year LFFS were 100% vs 98% (p=0.46) and 94% vs 96% (p=0.34), 5- and 10-year MFFS were 100% vs 100% and 100% vs 92% (p=0.004), and 5- and 10-year DFFS were 100% vs 98% at both time points (p=0.65 and p=0.67, respectively). <h3>Conclusion</h3> In this patient cohort, there was no local control benefit to larger GTV to PTV expansions. For patients with tumors not eligible for SRS, fractionated treatment using a rigorous stereotactic workflow with ≤ 3 mm PTV expansions is an effective approach for WHO grade I meningiomas.

Prognostic value of PD-L1 and Siglec-15 expression in patients with nasopharyngeal carcinoma

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). Here, we aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in nasopharyngeal carcinoma (NPC) patients. We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescence staining in 182 NPC tissue samples. A significant correlation was identified between the PD-L1 and Siglec-15 expression (P = 0.000). Moreover, Kaplan–Meier survival curves showed that PD-L1 expression was associated with improved overall survival (OS) (P = 0.025) and Siglec-15 expression was associated with improved distant failure-free survival (D-FFS) (P = 0.048). Moreover, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of OS (P = 0.020) and D-FFS (P = 0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression had significant advantages regarding OS, compared to other groups (P = 0.037). PD-L1 and Siglec-15 may represent novel biomarkers for predicting the prognosis of NPC patients. Siglec-15 may be considered as a potential target for the development of therapeutics for NPC treatment in the future.

Induction chemotherapy followed by radical chemoradiotherapy for patients with stage IV non-metastatic nasopharyngeal carcinoma: 11-Year Experience in a tertiary centre.

T4 nasopharyngeal carcinoma (NPC) with close proximity to critical organs at risk (OARs) is usually underdosed during radiotherapy in order to respect radiation constraints. N3 disease has high risk of distant metastasis. Induction chemotherapy (IC) provides advantages of sparing of OARs during subsequent chemoradiotherapy (CCRT) and early eradication of micrometastasis. However, factors predicting successes of IC in this patient group are not well-studied. 104 T4 or N3 NPC patients were retrospectively reviewed during 2007-2018. They were planned for IC followed by CCRT using intensity-modulated radiotherapy. In the whole group, five-year failure-free survival (FFS), locoregional failure-free survival (LRFS), distant failure-free survival (DFFS) and overall survival (OS) were 40.9%, 45.7%, 46.9% and 53.6% respectively. Isolated marginal failure rate was 5% (4/80) among patients with primary tumours located close to critical OARs. Pre-IC gross tumour volume primary (GTVp) total volume > 110 cm3 correlated with worse five-year LRFS (OR 6.37, P = 0.008), DFFS (OR 8.89, P = 0.003) and OS (OR 50.12, P < 0.001). In the T4 subgroup, IC improved D100% GTVp from 61.39 Gy to 64.71 Gy (P < 0.001) and V100% GTVp from 98.78% to 99.28% (P < 0.001). Our study demonstrated improved dosimetric parameters and low isolated marginal failure rate. It supported the use of IC and CCRT for tumours located close to critical OARs. Further research is warranted to compare predictive roles of pre- and post-IC tumour volumes. For high-risk patients being defined by pre-IC volume or other prognostic models, treatment escalation should be considered.

Multi-institutional matched comparison of radical cystectomy to trimodality therapy for muscle-invasive bladder cancer.

433 Background: Prior randomized controlled trials (RCT) comparing bladder preservation to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) closed early due to lack of accrual. Given that no future RCTs are foreseen, and in the absence of level 1 data, we aimed to provide the best evidence possible on outcomes of matched cohorts comparing trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to RC in order to guide management. Methods: This retrospective analysis included 703 patients with MIBC clinical stage T2-T3/4aN0M0 MIBC urothelial carcinoma of the bladder, 421 RC and 282 TMT who would have been eligible for both TMT or RC, treated at the Massachusetts General Hospital, Boston; Princess Margaret Cancer Centre, Toronto; and University of Southern California, Los Angeles between 2005-2017. To compare homogeneous cohorts, all patients included in this analysis had solitary tumors &lt; 7 cm, no or unilateral hydronephrosis, and no multifocal carcinoma in situ. Treatment propensity scores were estimated using logistic regression, and patients were matched 3:1 with replacement. Covariates included age, sex, clinical T stage, hydronephrosis, (neo)adjuvant chemotherapy, body mass index, smoking history, and ECOG status. Overall survival (OS) was estimated with adjusted Cox models; cancer-specific survival (CSS), distant failure-free survival, pelvic nodal failure-free survival and metastasis-free survival (combined distant and pelvic nodal failure) were estimated with adjusted competing risk models. Our primary endpoint of interest was metastasis-free survival. The analysis was performed as intent-to-treat. Results: The 3:1 matched cohort comprised of 1,116 patients (834 RC vs 282 TMT). After matching, age (71.3 vs 71.6), cT2 clinical stage (88 vs 90%), presence of hydronephrosis (12 vs 10%), and use of (neo)adjuvant chemotherapy (60 vs 65%) were similar between RC and TMT cohorts. Salvage cystectomy was performed in 38 patients (13%) treated by TMT. At 5 years, metastasis-free (73 vs 78%, p = 0.07), distant failure-free (78 vs 82%, p = 0.14), and pelvic nodal failure-free (96 vs 94%, p = 0.33) survival were not statistically different between RC and TMT, whereas CSS and OS favored TMT (78 vs 85%, p = 0.02; 70 vs 78%, p &lt; 0.001). Outcomes for RC and TMT were not different among centers. Final pT stage in the RC patients was: pT0 14%, pT1 7%, pT2 29%, pT3/4 42% and N+ 24%. Peri RC mortality was 2.1% and median number of nodes removed was 40. NMIBC recurrence occurred in 57/278 (20.5%) TMT patients. Conclusions: This large multi-institutional contemporary study provides the best evidence to date, in the absence of randomized trials, supporting TMT for select patients with MIBC. Oncologic outcomes seem to be equivalent between TMT and RC, affirming the position that TMT should be offered as an effective alternative.

Older cancer patients receiving radiotherapy: a systematic review for the role of sarcopenia in treatment outcomes.

Previous studies have evaluated the prognostic effects of sarcopenia in cancer patients receiving various treatments, including chemotherapy and surgery, but few studies have focused on radiotherapy (RT). We aimed to investigate the prevalence of sarcopenia and the relationship between sarcopenia and outcomes in older cancer patients who underwent RT without chemotherapy. A systematic review of the literature was conducted in Pubmed/Medline and Cochrane databases in September 2021. We used the search terms and medical subject heading terms "sarcopenia," "low muscle mass (LMM)," "low muscle strength," "LMM and low muscle strength," "LMM and low muscle strength and low physical performance," and "RT." Outcomes were overall survival (OS), progression-free survival, non-cancer death, cancer death, disease-specific survival, local failure-free survival, distant failure-free survival, and RT-related toxicities. Among 460 studies, 8 studies were eligible for inclusion. The prevalence of sarcopenia was between 42.8% and 72%. Sarcopenia was not associated with OS or OS at 3years in seven studies in which it was defined as the presence of LMM, while it was related in one study, in which it was defined as the concomitant presence of LMM and muscle strength/function. There was heterogeneity between the studies because there was diversity in their inclusion criteria, definition and assessment methods used for detection of sarcopenia, considered cutoffs for low muscle mass and strength, cross-sectional locations on imaging to assess muscle mass and included covariates. The discrepancy in the results of the studies may also result from the variations in diagnoses, sample sizes, and treatment modalities. The low number of included studies and a small number of patients in each study limited generalizability. Sarcopenia may be a prognostic factor, especially in OS when low muscle strength/function is integrated into its definition. We suggest that clinicians focus on muscle strength/function while considering sarcopenia and its association with cancer and RT-related outcomes.

Prognostic Relevance of Change in Body Mass Index in Patients With Nasopharyngeal Carcinoma Undergoing Volumetric Modulated Arc Therapy: A Retrospective Study.

ObjectiveTo assess the effect of pretreatment body mass index (BMI) and the extent of change in BMI (ΔBMI) during the treatment course on the treatment outcomes in patients with nasopharyngeal carcinoma (NPC) receiving volumetric modulated arc therapy (VMAT).MethodsData pertaining to 498 consecutive NPC patients with stage I–IVA disease who received VMAT between January 2010 and November 2011 at a single center were retrospectively analyzed. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the prognostic significance of pretreatment BMI and ΔBMI. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off point of ΔBMI.ResultsThe 5-year loco-regional failure-free (L-FFR), distant failure-free survival (D-FFR), disease-free survival (DFS), and overall survival (OS) rates were 90.6%, 83.7%, 71.5% and 79.3%, respectively. The 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with ΔBMI ≤1 kg/m2 vs ΔBMI >1 kg/m2 were 92.3% vs 89.3% (P = .137), 90.9% vs 78.5% (P < .001), 80.4% vs 65.1% (P < .001), and 88.0% vs 73.0% (P < .001), respectively. ΔBMI >1 kg/m2 was an independent predictor of D-FFR (P = .002), DFS (P = .002), and OS (P = .001).ConclusionsΔBMI during treatment course may have a significant impact on the prognosis of NPC patients receiving VMAT.

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial

Objective: The objective of this trial is to evaluate and compare the acute toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with docetaxel plus cisplatin, or docetaxel, or cisplatin concurrently with helical tomotherapy during concurrent chemoradiotherapy (CCRT). Methods: In a prospective, single-center, open-label, randomized phase II study, after 2 cycles of induction chemotherapy with docetaxel plus cisplatin regimen, 125 patients with LA-NPC (stage III and IVA, UICC eighth) diagnosed pathologically from June 2017 to November 2019 were randomized into CCRT with docetaxel plus cisplatin group (25 patients), CCRT with docetaxel group (50 patients), and CCRT with cisplatin group (50 patients). The incidence of grade 3 or 4 acute toxicities and clinical efficacy were analyzed among the 3 groups. Results: Safety evaluation was completed in all the 125 patients, during the CCRT period, 66.4% of patients completed 3 cycles of chemotherapy, 24.0% completed 2 cycles of chemotherapy, and 9.6% completed 1 cycle of chemotherapy according to the research plan. The incidence of grade 3 or 4 acute toxicity in CCRT with docetaxel plus cisplatin (DP), docetaxel (D), and cisplatin (P) groups was 88.0%, 72.0%, and 56.0%, respectively. The incidence of grade 3 or 4 acute toxicities in the DP group was significantly higher than that in the D and P groups (P = .015), no significant difference was detected between the D and P groups (P = .096). The most common toxicities were mucositis (40.0%), leukopenia (29.6%), neutropenia (26.4%), and pharyngo-esophagitis (12.0%); compared to D and P groups, DP group did not significantly improved the 3-year overall survival (96.0% vs 87.0% and 87.6%), progression-free survival (92.0% vs 79.7% and,76.9%), locoregional failure-free survival (96.0% vs 91.8% and 92.7%), and distant failure-free survival (100% vs 90.0% and 89.0%), there were no significant difference in survival data among the 3 groups (all P > .05). Conclusions: Higher survival benefits did not achieve from intensified CCRT with DP, CCRT with P or D obtained similar short-term survival outcomes with similar acceptable toxicities in LA-NPC patients.

Clinical analysis of multimodal treatment for localized synovial sarcoma: A multicenter retrospective study

IntroductionSeveral prognostic factors for survival in synovial sarcoma have been proposed, but the role of adjuvant chemotherapy and radiotherapy is a matter of debate. The study aim was to clarify the effect of high-dose ifosfamide-containing chemotherapy and adjuvant radiotherapy for patients with localized synovial sarcoma. Materials and methodsFive tertiary musculoskeletal oncology hospitals participated in this retrospective study. The records of the patient diagnosed with synovial sarcoma without metastasis at diagnosis from 1990 to 2011 have been collected and reviewed. Overall, distant failure-free, and local failure-free survivals were calculated, and prognostic factors for each survival were evaluated by performing univariate and multivariate analyses. ResultsA total of 162 patients were enrolled in this study with a median follow-up period of 67 months (range, 5–267 months) for all surviving patients. The 5-year overall, distant failure-free, and local failure-free survival rates were 79.7%, 66.3%, and 98.4%, respectively. Univariate analyses demonstrated that high-dose ifosfamide-containing chemotherapy was significantly associated with better overall (p = 0.014) and distant failure-free survival (p = 0.0043) than that of low-dose or no ifosfamide-containing chemotherapy if we analyzed only patients with tumors >5 cm in size. Addition of radiotherapy was not a significant prognostic factor for overall survival in the univariate and multivariate analyses, but it did improve the overall survival of the patients with R1 resection (p = 0.053). ConclusionPatients with localized synovial sarcoma >5 cm in size had better overall and distant failure-free survival after receiving adjuvant chemotherapy containing high-dose ifosfamide comparing to low-dose or no ifosfamide-containing chemotherapy. The addition of adjuvant radiotherapy was beneficial for the patients who received R1 resection. Alternatively, adjuvant radiotherapy could be avoided for patients who achieved an R0 margin.

Tumor Control and Survival Outcomes Based on Maximum Standardized Uptake Value on FDG-PET/CT in T1-2 NSCLC Treated With SBRT

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is standard of care in medically inoperable early-stage non-small cell lung cancer (NSCLC). Assessment of maximum standardized uptake value (SUVmax) on FDG-PET/CT before and after SBRT may stratify tumor control and survival outcomes. <h3>Materials/Methods</h3> Retrospective chart review identified patients with T1-2N0M0 NSCLC who were only treated with SBRT between 2012 and 2019. Pretreatment SUVmax and percent change in SUVmax at 3 and 6 months following SBRT were assessed as independent predictors of local control (LC), regional failure-free survival (RFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS). Receiver operator characteristic (ROC) analysis yielded optimal cut points for comparison. Survival analyses were performed with Kaplan-Meier estimates with log rank testing, and Cox proportional hazards models including age, sex, T stage, histology, and performance status. <h3>Results</h3> 71 (43.6%) out of 163 patients underwent repeat PET/CT within 6 months of SBRT completion. Median follow-up was 19 months (range 1 – 94 months). For the whole cohort, 1-year and 2-year LC, PFS, and OS were 95.0% and 80.3%, 75.9% and 47.7%, and 87.1% and 67.0%, respectively. For DFFS, pretreatment SUVmax greater than 4 had an aHR of 3.33 (95% CI 1.42 – 7.84, <i>P</i> = 0.006). Pre-SBRT SUVmax over 12.3 had an aHR of 2.80 (95% CI 1.3 – 6.2, <i>P</i> = 0.011) for PFS, and a cut point of 12.6 had an aHR of 3.00 (95% CI 1.6 – 5.8, <i>P</i> = 0.003) for OS. Pretreatment SUVmax did not significantly predict LC or RFFS. At 3 months following SBRT, an SUVmax decrease of at least 45% was associated with improved LC (aHR = 0.15, 95% CI 0.02 – 0.91, <i>P</i> = 0.018). A 6-month SUVmax decrease of more than 53% was associated with better LC (<i>P</i> = 0.038), and a decrease over 11% was associated with improved RFFS (aHR = 0.12, 95% CI 0.02 – 0.96, <i>P</i> = 0.046). Change in SUVmax was not significantly associated with DFFS, PFS, or OS at either time point. No factors other than performance status for PFS and OS were significant. <h3>Conclusion</h3> At 3 and 6 months following SBRT, cut points for percentage change in SUVmax can stratify risk of local recurrence and possibly regional recurrence. Pretreatment SUVmax cutoffs can predict distant failure, progression-free survival, and overall survival in early-stage NSCLC.

Volumetric modulated arctherapy for locally advanced nasopharyngeal carcinoma: Clinical efficacy and late toxicity

PurposeWe report our experience of 86 consecutive patients with locally advanced nasopharyngeal carcinoma who were treated with volumetric modulated arc therapy. Materials and methodsWe retrospectively reviewed the medical records of 86 patients with histologically proven primary nasopharyngeal carcinoma treated with volumetric modulated arctherapy technique radiotherapy. Primary endpoints were local, regional, distant control, and overall survival, second endpoint was late toxicity. ResultsThe median age was 47.5 years (range: 13–79 years) with sex ratio 1.09. At diagnosis, rhinologic symptoms represented the most common clinical presentation, reported by 61 patients (70.9%). Almost 88.4% of patients presented non-keratinizing undifferentiated carcinoma histology (n=76). Most of the patients presented a locally advanced disease defined by stage III and IVa (95.3%). Therefore, 31 patients were treated by concurrent chemoradiation (36%), 52 patients received induction chemotherapy followed by concurrent chemoradiotherapy (57%), three patients received induction chemotherapy followed by exclusive radiotherapy (3.5%). and three patients treated with exclusive irradiation (3.5%). With a median follow up of 15.7 months (range: 4–33.3 months), nine patients died (10.4%), three presented local or locoregional relapse (3.4%), while nine patients presented distant recurrences (10.4%). The two years overall and disease-free survival rates were 88.7% and 83.1% respectively, locoregional control was 100% at 12 months and 96.2% at 24 months, and the two years distant failure-free survival was 86.7%. Time to relapse was the only prognostic factor in univariate analysis for overall survival in our study. The therapeutic tolerance was good with 61.7% of grade 3 and 2.3% grade 4 hyposialia respectively, 46.5% of otological disorders and no radionecrosis was noted. ConclusionVolumetric modulated arctherapy technique with concurrent chemoradiotherapy is an effective treatment for nasopharyngeal carcinoma with excellent overall and locoregional control without severe toxicity. Distant metastasis is the major site of failure, so induction chemotherapy added to chemoradiotherapy must be discussed in multidisciplinary consultation meeting because it significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone.