Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

Initial treatment and survival in Danish patients diagnosed with non-small-cell lung cancer (2005-2015): SCAN-LEAF study.

Aim: To describe initial treatment patterns and survival of patients diagnosed with non-small-cell lung cancer (NSCLC) in Denmark, before immune checkpoint inhibitor and later-generation tyrosine kinase inhibitor use. Patients & methods: Adults diagnosed with incident NSCLC (2005-2015; follow-up: 2016). Initial treatments and overall survival (OS) are reported. Results: 31,939 NSCLC patients (51.6% stage IV) were included. Increasing use of curative radiotherapy/chemoradiation for stage I, II/IIIA and IIIB NSCLC coincided with improved 2-year OS. Systemic anticancer therapy use increased for patients with stage IV non-squamous NSCLC (53.0-60.6%) but not squamous NSCLC (44.9-47.3%). 1-year OS improved in patients with stage IV non-squamous NSCLC (23-31%) but not squamous NSCLC (22-25%). Conclusion: Trends indicated improved OS as treatments evolved between 2005 and 2015, but the effect was limited to 1-year OS in stage IV disease.

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP).

INTRODUCTION: In contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives. MATERIAL AND METHODS: Between January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval. RESULTS: Depending on the median time interval of 55 days (d) (95% CI 51.42-84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%). Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months). The 5-year OS rate for all patients involved was 71% (95% CI 0.55-0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48-1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42-0.80; X2(1) = 1.16, p = 0.281). Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75-0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89-1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57-0.95; X2(1) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59-0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63-0.94) and thus not significantly different from 65% (95% CI 0.45-0.85) of the group ≥55 d; (X2(1) = 0.29, p = 0.589). CONCLUSIONS: The results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.

Patterns and timing of recurrence in esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy plus esophagectomy.

BACKGROUND: Tumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT. METHODS: A total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT. RESULTS: The 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant. CONCLUSIONS: NACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).

Adjuvant treatment and outcomes for patients with stage IIIA grade 1 endometrioid endometrial cancer.

OBJECTIVE: The role and type of adjuvant therapy for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIA grade 1 endometrioid endometrial adenocarcinoma are controversial. This retrospective cohort study aimed to determine associations between adjuvant therapy use and survival among patients with stage IIIA grade 1 endometrial cancer. METHODS: Patients who underwent primary surgery for stage IIIA (FIGO 2009 staging) grade 1 endometrial cancer between January 2004 and December 2016 were identified in the National Cancer Database. Demographics and receipt of adjuvant therapy were compared. Overall survival was analyzed using Kaplan-Meier curves, log-rank test, and multivariable Cox proportional hazard models. RESULTS: Of 1120 patients, 248 (22.1%) received no adjuvant treatment, 286 (25.5%) received chemotherapy alone, 201 (18.0%) radiation alone, and 385 (34.4%) chemotherapy and radiation. Five-year overall survival rate was 83.0% (95% CI 80.1% to 85.6%). Older age, increasing comorbidity count, and lymphovascular space invasion status were significant negative predictors of survival. Over time, there was an increasing rate of chemotherapy (45.4% in 2004-2009 vs 69.2% in 2010-2016; p<0.001). In the multivariable analysis, chemotherapy was associated with significantly improved overall survival compared with no adjuvant therapy (HR 0.49 (95% CI 0.31 to 0.79); p=0.003). There was no survival association when comparing radiation alone with no treatment, and none when adding radiation to chemotherapy compared with chemotherapy alone. Those with lymphovascular space invasion (n=124/507) had improved overall survival with chemotherapy and radiation (5-year overall survival 91.2% vs 76.7% for chemotherapy alone and 27.3% for radiation alone, log-rank p<0.001), but there was no survival difference after adjusting for age and comorbidity (HR 0.25 (95% CI 0.05 to 1.41); p=0.12). CONCLUSIONS: The use of adjuvant chemotherapy for the treatment of stage IIIA grade 1 endometrial cancer increased over time and was associated with improved overall survival compared with radiation alone or chemoradiation. Patients with lymphovascular space invasion may benefit from combination therapy.

Practice patterns and survival in FIGO 2009 stage 3B endometrial cancer.

OBJECTIVE: To describe the practice patterns and outcomes of patients with stage 3B endometrial cancer. METHODS: We queried the National Cancer Database for all surgically staged, stage 3 patients between 2012 and 2016. Patients who received any pre-operative therapy were excluded. Demographics, tumor factors, and adjuvant therapy for the stage 3 substages were compared. Logistic regression was used to identify factors associated with adjuvant therapy. Kaplan Meier curves were generated and compared using the log-rank test. Multivariable Cox Proportional Hazards Model was used to adjust for prognostic factors. Findings with p < 0.05 were considered significant. RESULTS: Of 7363 patients with stage 3 disease, 478 (6%) had stage 3B; 1732 (23%) had stage 3A, 3457 (48%) had stage 3C1, and 1696 (23%) had stage 3C2 disease. Post-surgical treatment consisted of: combined chemotherapy (CT) and radiation (RT) (49%), CT alone (28%), RT alone (9%), 14% received no postoperative therapy. Among all stage 3 substages, patients with stage 3B disease were the least likely to receive any CT, and the most likely to receive RT alone. After adjusting for known prognostic factors, patients with stage 3A (Hazard ratio (HR) of death = 0.64) and 3C1 (HR of death = 0.79) disease had significantly worse overall survival compared to stage 3B; survival was not demonstrably different from patients with stage 3C2 disease. Patients with stage 3B disease who received CT + RT had the best overall survival. CONCLUSION: Survival of patients with stage 3B disease is similar to that of patients with para-aortic node metastases and is inferior to all others with stage 3 endometrial cancer. Less frequent CT and a higher rate of post-operative RT alone, describes a distinct practice from that seen in other stage 3 patients.

Perioperative change in neutrophil count predicts worse survival in esophageal squamous cell carcinoma.

Aims: This study aimed to investigate the relationship between perioperative change in neutrophil count and survival of patients with esophageal squamous cell carcinoma. Method: Neutrophil change (Nc) (where Nc = post-surgery neutrophil count - pre-surgery neutrophil count) was counted according to data within 1 week before surgery and 2 weeks after surgery. Patients were divided into two groups, Nc ≥2.60 and Nc <2.60, according to the median of Nc. Results: Multivariate analysis revealed that Nc ≥2.60 was an independent prognostic marker for overall survival. Subgroup analysis suggested that the overall survival of male patients, patients aged ≤60 years, patients without vessel invasion and patients without nerve infiltration was dramatically worse for those with Nc <2.60. Conclusion: Perioperative change in neutrophil count predicts worse survival in esophageal squamous cell carcinoma after surgery.

Salvage Following Transoral Laser Microsurgery for Early Glottic Cancer in National Veteran Database.

OBJECTIVES: Transoral laser microsurgery (TLM) is commonly utilized for early glottic cancer and offers favorable oncologic and functional outcomes. However, the survival implications of salvage therapy for recurrent or persistent disease have not been definitively characterized. STUDY DESIGN: Retrospective, national database cohort study. METHODS: Data were extracted from Veterans Health Affairs (VHA) Informatics and Computing Infrastructure (VINCI) concerning the TLM-based management of T1-T2 glottic squamous cell carcinoma patients between 2000 and 2017. Patients were characterized as either requiring TLM-only, or in cases of persistent or recurrent local disease, TLM plus change in treatment modality (radiotherapy, chemoradiotherapy, or open surgery). Predictors of overall survival (OS), cancer-specific survival (CSS), and salvage-free survival were evaluated via Cox and Fine-Gray models. RESULTS: About 553 patients (70.9% T1a, 13.4% T1b, 15.7% T2) were included, with a median follow-up time of 74.5 months. The need for non-TLM salvage increased along with more advanced disease (11.7% T1a, 29.7% T1b, 32.2% T2). Compared to patients with T1a disease, those with T1b and T2 tumors initially treated with TLM had a significantly higher probability of receiving non-TLM salvage (T1b: HR 2.70, 95% CI: 1.61-4.54; T2: HR 3.02, 95% CI: 1.88-4.84). In a multivariable model, receipt of non-TLM salvage was not a significant predictor of either OS (HR = 0.91, 95% CI: 0.62-1.33, P = .624) or CSS (HR 1.21 95% CI 0.51-2.86, P = .667). CONCLUSION: The majority of patients with early glottic cancer that are managed with TLM do not require additional salvage therapy. When non-TLM salvage was required, there was no decrement in OS or CSS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2766-2772, 2021.

Locoregional Recurrence in p16-Positive Oropharyngeal Squamous Cell Carcinoma After TORS.

OBJECTIVE: To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). STUDY DESIGN: Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCN-guideline-compliant adjuvant therapy at a single institution from 2007 to 2017. METHODS: Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease-free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments. RESULTS: Of 541 patients who completed guideline-indicated therapy, the estimated 5-year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09-0.83], P = .023), but there was no difference in DFS (P = .21) and OS (P = .86) between adjuvant therapy groups. The 5-year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P < .001). Patients who initially received adjuvant chemoradiation and those suffering local, in-field, and/or retropharyngeal node recurrences had decreased disease control after salvage therapy. CONCLUSION: LRR rates are low for HPV+ OPSCCs completing TORS and guideline-compliant adjuvant therapy. Patients without indication for adjuvant therapy more often suffer LRR, but these recurrences are generally controllable by salvage therapy. Improved understanding of the patterns of recurrence most amenable to salvage therapy may guide treatment decisions, counseling, and adjuvant therapy de-escalation trials. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2865-E2873, 2021.

Comparison of therapeutic effects of chemo-radiotherapy with neoadjuvant chemotherapy before radical surgery in patients with bulky cervical carcinoma (stage IB3 & IIA2).

BACKGROUND: Cervical cancer is one of the most common malignancies among women. Appropriate and timely treatment of these patients can reduce the complications and increase their survival. The objective of this study was to compare neoadjuvant chemotherapy plus radical hysterectomy (NACTRH) and chemo-radiotherapy (CRT) in patients with bulky cervical cancer (stage IB3 & IIA2). MATERIAL AND METHODS: The medical records of patients with bulky cervical cancer (stage IB3 & IIA2) that received NACTRH or CRT between 2007 and 2017 were evaluated for therapeutic effects. Demographic characteristics, complications of chemo-radiotherapy and neoadjuvant chemotherapy, were collected in a researcher-made questionnaire. Our primary outcome was comparison of overall survival (OS), and disease-free survival (DFS) between two groups receiving NACTRH and CRT modalities. RESULTS: One-hundred and twenty three patients were enrolled in the study. The median age and the proportion of patients with stage IIA2 were higher in the CRT group compared to the NACTRH group (p < 0.05). The medians (95% CI) OS were 3.64 (3.95-6.45) and 3.9 (3.53-4.27) years in the NACTRH and CRT groups, respectively (P = 0.003). There were 16 (34.8%) and 22 (43.1%) recurrences in the NACTRH and CRT group, respectively (P = 0.4). The median (95% CI) DFS was 4.5 (3.88-5.12) years in the NACTRH group and 3.6 (2.85-4.35) years in the CRT group (P = 0.004). The 3-year OS rate in NACTRH and CRT groups were 97 and 90% respectively. The 3-year DFS rate in NACTRH and CRT groups were 88 and 66% respectively. CONCLUSIONS: NACTRH is associated with a higher OS and DFS compared to CRT.

Non-exenterative surgical management of recurrent endometrial carcinoma.

OBJECTIVE: To examine the role of non-exenterative secondary cytoreductive surgery (SCS) compared with non-surgical treatments and identify predictors of improved survival for patients with recurrent endometrial cancer (EC). METHODS: All patients undergoing primary surgical management for EC 1/1/2009-12/31/2017 who subsequently developed recurrence were retrospectively identified. Survival was determined from date of diagnosis of first recurrence to last follow-up and estimated using Kaplan-Meier method. Differences in survival were analyzed using Log-rank and Wald tests, based on Cox Proportional Hazards model. RESULTS: Among 376 patients with recurrent EC, median time to recurrence was 14.3 months (range, 0.2-102.2), post-recurrence median survival 29 months, median follow-up 29.2 months (range, 0-116). Sixty-one patients (16.2%) received SCS, 257 (68.4%) medical management (MM) (chemotherapy and/or radiation therapy), 32 (8.5%) hormonal therapy, 26 (6.9%) no further therapy. Patients selected for SCS were younger, had more endometrioid histology, more stage I disease at initial diagnosis, no residual disease after primary surgery, longer interval to first recurrence or progression, and the longest OS (57.6 months) (95% CI, 33.3-not reached). On multivariate analysis SCS was an independent predictor of improved survival. Among the 61 SCS patients, age < 70 at time of initial diagnosis, and endometrioid histology, were associated with improved post-relapse survival univariately (p = 0.008, 0.03, respectively). CONCLUSIONS: While MM was the most common treatment for first recurrence of EC, patients selected for surgery demonstrated the greatest survival benefit even after controlling for tumor size, site, histology, stage, time to recurrence. Careful patient selection and favorable tumor factors likely play a major role in improved outcomes. Surgical management should be considered whenever feasible in medically eligible patients, with additional consideration given to our suggested criteria.

Tamoxifen. A treatment for meningioma?

BACKGROUND: No large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken. METHODS: We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningiomas operated between 2007 and 2017. Survival analyses were performed using a matched cohort study. RESULTS: 251 patients treated by tamoxifen were extracted from a nationwide population-based cohort of 28 924 patients operated on for a meningioma over a 10-year period. 94% were female and median age at meningioma first surgery was 57 years IQR[47-67]. Tamoxifen treatment median duration was 1.4 years IQR[0.4-3.2]. Tamoxifen treatment median cumulative given dose was 11.4 gs, IQR[3.6-24.9]. There was a strong positive correlation between treatment duration and cumulative dose (τ=0.81, p<0.001). 6% of the patient had to be reoperated for a meningioma recurrence and 26.3% had radiotherapy. OS rates at 5 and 10 years were: 92.3%, 95%CI[90.3-94.3] and 81.3%, 95%CI[75.2-88] respectively. These 251 patients were matched by gender, age at surgery and grade with the same number of subjects within the nationwide cohort. Nor overall (HR=1.46, 95%CI[0.86- 2.49], p=0.163) or progression-free survival (HR=1.2, 95%CI[0.89- 1.62], p=0.239) were significantly improved by the tamoxifen treatment. CONCLUSION: Using this unique database, in the setting of breast cancer, we could not conclude on a favourable effect of tamoxifen to prevent recurrence after meningioma surgery or to increase meningioma-related survival even in case of prolonged treatment duration or high cumulative given dose.

15-Year Experience with Multimodality Therapy Including Esophagectomy for Elderly Patients with Locoregional Esophageal Cancer.

BACKGROUND: Optimal curative therapy for locally advanced esophageal and esophagogastric junction (EGJ) cancer might not be offered to elderly patients due to patient and treating physician perception of the high risk of therapy. To understand the risk of multimodality curative therapy, including surgical resection in the elderly population, we studied our experience with curative therapy in this patient population and compared the risks and outcomes with those in a younger population. STUDY DESIGN: Between January 1, 2004 and December 31, 2019, four hundred and five consecutive patients with esophageal or EGJ cancer underwent primary treatment at our institution, including esophagectomy. Data collected included demographic information, tumor stage, preoperative Charlson Comorbidity Index scores, treatment variables, and short- and long-term outcomes. Patients who were 70 years or older were classified as the "older" group and patients younger than 70 years were "younger." RESULTS: One hundred and eighty-eight younger (mean age 59 years) and 94 older (mean age 74 years) patients received neoadjuvant chemoradiotherapy and surgical resection for stage II and higher cancer. Preoperative American Society of Anesthesiologist and Charlson Comorbidity Index scores were significantly worse in the older group. Postoperative atrial fibrillation and urinary retention developed more often in the older group. Despite this, the rate of postoperative Clavien-Dindo complication severity scores of 3 or higher, perioperative mortality rates, and lengths of stay were similar. Long-term age-adjusted survival rate was 44.8% at 5 years for the group 70 years or older and 39% for the group younger than 70 years (NS). CONCLUSIONS: Patients 70 years and older with locally advanced esophageal or EGJ cancer should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection. Although preoperative risk scoring and postoperative atrial arrythmias are higher in the older group, short- and long-term outcomes are not inferior in these patients.

Effects of Adjuvant Therapy Compliance and Anastomotic Leakage on the Oncologic Outcomes of Patients With Rectal Cancer After Curative Resection.

BACKGROUND: Anastomotic leakage might be directly or indirectly related to the prognosis of patients with rectal cancer. OBJECTIVE: This study aimed to investigate whether anastomotic leakage affects the oncologic outcomes in patients with rectal cancer. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a teaching hospital between January 2009 and December 2013. PATIENTS: Patients who underwent curative resection for primary rectal cancer were included. MAIN OUTCOME AND MEASURE: Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival. RESULTS: The overall incidence of anastomotic leakage was 2.7% (107/3865). Local recurrence was more frequent in patients with anastomotic leakage than in those without (14.0% vs 6.7%; p = 0.007). By multivariate analysis, anastomotic leakage was associated with increased local recurrence rate (p = 0.014) and poorer overall survival (p = 0.011). In subgroup analysis, compared with other pathologic risk factors, anastomotic leakage was associated with higher occurrence of local and distant recurrence in patients with stage II rectal cancer (p = 0.031 and <0.001). In patients with stage III rectal cancers, adjuvant therapy was more likely to be delayed or canceled in those experiencing anastomotic leakage (63 vs 39 d, p < 0.001; 37.3% vs 66.7%, p < 0.001). In addition, this patient group had the worst survival outcome when compared with those without anastomotic leakage and those with timely adjuvant therapy (5-year disease-free survival rate, p = 0.013; 5-year overall survival rate, p = 0.001). LIMITATIONS: This study is limited by its retrospective nature. CONCLUSIONS: There was a robust association between anastomotic leakage and local recurrence, while also potentially affect long-term survival of the patient group. Delayed or cancelled adjuvant therapy administration because of anastomotic leakage may partly account for the poorer survival in those patients with advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B459. EFECTOS DE OBSERVANCIA DE TERAPIA ADYUVANTE Y FUGA ANASTOMTICA, EN RESULTADOS ONCOLGICOS DE PACIENTES CON CNCER RECTAL, DESPUS DE UNA RESECCIN CURATIVA: ANTECEDENTES:La fuga anastomótica podría estar relacionada directa o indirectamente, con el pronóstico de los pacientes con cáncer de recto.OBJETIVO:El estudio tuvo como objetivo investigar si la fuga anastomótica afecta los resultados oncológicos, en pacientes con cáncer de recto.DISEÑO:Fue un análisis retrospectivo de datos recolectados prospectivamente.AJUSTE:El estudio se realizó en un hospital universitario entre enero de 2009 y diciembre de 2013.PACIENTES:Pacientes sometidos a resección curativa por cáncer rectal primario.PRINCIPALES MEDIDAS DE RESULTADO:Se utilizaron análisis de Kaplan-Meier para evaluar la supervivencia libre de enfermedad y supervivencia general.RESULTADOS:La incidencia global de fuga anastomótica fue del 2,7% (107/3865). La recurrencia local fue más frecuente en pacientes con fuga anastomótica, que en aquellos sin ella (14,0% frente a 6,7%, p = 0,007). Por análisis multivariado, la fuga anastomótica se asoció con una mayor tasa de recurrencia local (p = 0,014) y una peor supervivencia general (p = 0,011). En el análisis de subgrupos, en comparación con otros factores de riesgo patológicos, la fuga anastomótica se asoció con una mayor incidencia de recidiva local y a distancia en pacientes con cáncer rectal en estadio II (p = 0,031 y <0,001, respectivamente). En pacientes con cáncer rectal estadio III, la terapia adyuvante tuvo más probabilidades de retrasarse o cancelarse en aquellos que sufrían fuga anastomótica (63 vs 39 días, p <0,001; 37,3% vs 66,7%, p <0,001). Y este grupo de pacientes tuvo el peor resultado de supervivencia en comparación con aquellos sin fuga anastomótica y aquellos con terapia adyuvante oportuna (tasa de supervivencia libre de enfermedad a 5 años, p = 0,013; tasa de supervivencia global a 5 años, p = 0,001).LIMITACIONES:El estudio está limitado por su naturaleza retrospectiva.CONCLUSIONES:Hubo una sólida asociación entre la fuga anastomótica y la recurrencia local, mientras que también afecta potencialmente la supervivencia a largo plazo, del grupo de pacientes. La administración de terapia adyuvante retrasada o cancelada debido a una fuga anastomótica, puede explicar en parte, la menor supervivencia en aquellos pacientes con cáncer rectal avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B459.

Nomograms to predict lung metastasis probability and lung metastasis subgroup survival in malignant bone tumors.

The aim of this study was to construct and validate nomograms for predicting lung metastasis and lung metastasis subgroup overall survival in malignant primary osseous neoplasms. Least absolute shrinkage and selection operator, logistic and Cox analyses were used to identify risk factors for lung metastasis in malignant primary osseous neoplasms and prognostic factors for overall survival in the lung metastasis subgroup. Further, nomograms were established and validated. A total of 3184 patients were collected. Variables including age, histology type, American Joint Committee on Cancer T and N stage, other site metastasis, tumor extension and surgery were extracted for the nomograms. The authors found that nomograms could provide an effective approach for clinicians to identify patients with a high risk of lung metastasis in malignant primary osseous neoplasms and perform a personalized overall survival evaluation for the lung metastasis subgroup.

Survival Impact of Surgical Resection in Locally Advanced T4b Oral Squamous Cell Carcinoma.

OBJECTIVE/HYPOTHESIS: With non-surgical treatment, T4b oral squamous cell carcinoma (OSCC) have an unacceptably poor prognosis. A subset of patients if selected wisely for surgery, can have significantly improved survival. The present study aims to explore the feasibility of radical resection and neoadjuvant chemotherapy (NACT) in the T4b OSCC and their impact on survival, along with the factors affecting it. STUDY DESIGN: This is a retrospective analysis of 302 consecutive patients with T4b OSCC presented at our institute between July 2015 and January 2016. METHODS: Three different treatment protocols were decided depending on the extent of the disease-upfront resection, NACT (followed by surgery or chemo/radiation depending on the response), or upfront non-surgical treatment (chemotherapy and/or radiotherapy). RESULTS: Upfront surgery was done in 67 (22.19%) patients and 155 (51.32%) patients received NACT. The rest of the patients received upfront non-surgical treatment. The overall response rate of NACT was 23.23% and the resectability rate was 36.13%. The median OS for the whole population was 12 months (30 months for the surgical group and 9 months for the non-surgical group). There was no survival difference between supra versus infra-notch tumors (P value = .552) or post-NACT versus upfront surgery (P value = .932). Nodal involvement was the most important poor prognostic factor affecting both DFS (P = .006) and OS (P = .002). CONCLUSIONS: With proper patient selection after thorough clinico-radiological assessment, a subset of T4b OSCC can be operated with curative intention; either upfront or after downstaging with NACT, which ultimately translates into improved survival. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2266-E2274, 2021.

Evaluating the Impact of ESPAC-1 on Shifting the Paradigm of Pancreatic Cancer Treatment.

BACKGROUND: In 2004, the European Study Group for Pancreatic Cancer (ESPAC)-1 long-term data concluded that adjuvant chemotherapy provided a survival benefit for patients with pancreatic ductal adenocarcinoma (PDAC), whereas adjuvant chemoradiation was associated with worse overall survival. In this study, we investigated how long it took for US practice patterns to change following this trial. METHODS: The National Cancer Database was used to identify patients with stage I-III PDAC who underwent R0 or R1 resection followed by adjuvant chemotherapy or chemoradiation between 1998 and 2015. A multivariate analysis was performed to determine predictors of receiving adjuvant chemoradiation in the post-ESPAC-1 era. RESULTS: Between 1998 and 2015, adjuvant chemotherapy use increased from 2.9% to 51.6%, whereas adjuvant chemoradiation decreased from 49.5% to 22.9%. In 2010, adjuvant chemotherapy utilization surpassed that of chemoradiation. For patients diagnosed in the post-ESPAC-1 era, adjuvant chemotherapy (n = 7733) and chemoradiation (n = 6969) groups were compared. Patients who underwent adjuvant chemoradiation were younger, had private insurance, underwent surgery at nonacademic centers, and had more pathologically advanced cancers (all P < 0.01). After 2010, R1 resection was the strongest independent predictor of adjuvant chemoradiation use by multivariate analysis (OR 2.05, CI 1.8-2.3, P < 0.01). CONCLUSIONS: Adjuvant chemotherapy use exceeded that of adjuvant chemoradiation 6 y after the final publication of ESPAC-1 in 2004, highlighting the challenges of disseminating and adopting clinical data. After 2010, R1 disease was the most significant predictor of receiving adjuvant chemoradiation. Prospective studies are underway to definitively address the role of adjuvant chemoradiation in PDAC.

Serial Circulating Tumor DNA in Predicting and Monitoring the Effect of Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer: A Prospective Multicenter Study.

PURPOSE: We investigated the value of circulating tumor DNA (ctDNA) in predicting tumor response to neoadjuvant chemoradiotherapy (nCRT), monitoring tumor burden, and prognosing survival in patients with locally advanced rectal cancer (LARC). EXPERIMENTAL DESIGN: This prospective multicenter trial recruited 106 patients with LARC for treatment with nCRT followed by surgery. Serial ctDNAs were analyzed by next-generation sequencing at four timepoints: at baseline, during nCRT, presurgery, and postsurgery. RESULTS: In total, 1,098 mutations were identified in tumor tissues of the 104 patients being analyzed (median, seven mutations/patient). ctDNA was detected in 75%, 15.6%, 10.5%, and 6.7% of cases at the four timepoints, respectively. None of the 29 patients with pathologic complete response (ypCR) had preoperative ctDNA detected. The preoperative ctDNA-positive rate was significantly lower in the well-responded patients with pathologic tumor regression grade of ypCAP 0-1 than ypCAP 2-3 group (P < 0.001), lower in ypCR than non-ypCR group (P = 0.02), and lower in pathologic T stage (ypT) 0-2 than ypT 3-4 group (P = 0.002). With a median follow-up of 18.8 months, 13 patients (12.5%) experienced distant metastasis. ctDNA positivity at all four timepoints was associated with a shorter metastasis-free survival (MFS; P < 0.05). Multivariate analyses showed that the median variant allele frequency (VAF) of mutations in baseline ctDNA was a strong independent predictor of MFS (HR, 1.27; P < 0.001). CONCLUSIONS: We show that ctDNA is a real-time monitoring indicator that can accurately reflect the tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of MFS.

Pathological Predictors of Response to Neoadjuvant Treatment in Rectal Carcinoma.

PURPOSE: Neoadjuvant chemoradiotherapy has now become a standard treatment for rectal cancer. Recently, attempts have been made to predict the response rate to this treatment to decide whether or not it must be performed. However, tissue factors for predicting the response rate is not cohesively reviewed. METHODS: Eighty-three patients with rectal cancer, all under neoadjuvant chemoradiotherapy and subsequent surgery, were examined for tissue factors in the biopsy sample. The tissue factors examined include tumor differentiation grade, lymphovascular invasion, perineural invasion, pathological stage, and lymphocytic infiltration. Lymphocytic infiltration was investigated by immunohistochemistry for CD8 T lymphocyte in biopsy samples. RESULTS: In this study, tissue factors were found to play a decisive role in predicting response to neoadjuvant treatment. The most important factor was the pathological stage, which has the highest correlation with response to treatment. There is a significant relationship between CD8 lymphocyte infiltration and response to treatment (P value = 0.018). Primary perineural invasion and lymphovascular invasion also have a significant meaningful relationship with response to treatment (P value = 0.021 and P value = 0.036). CONCLUSION: In this study, it was determined that the investigated factors have a significant relationship with response to treatment and could be used to predict the response to treatment, and if a low possibility of positive response exists, prevention of the complications of neoadjuvant chemoradiotherapy for the patients could occur.