Distant Metastasis-free Survival Rates Research Articles

Predictive risk factors for distant metastasis in pediatric differentiated thyroid cancer from Saudi Arabia.

Despite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited. Medical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated. DM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (≤15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and post-operative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p < 0.0001). Higher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC.

Long-Term Results of Induction Chemotherapy for Esophageal Squamous Cell Carcinoma Receiving Concurrent Chemoradiotherapy

This study aimed to investigate the long-term clinical outcomes and toxicities of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with esophageal squamous cell carcinoma (ESCC). Between 2008 and 2022, 271 ESCC patients who received definitive CCRT (IC followed by CCRT, n = 72; CCRT alone, n = 199) were enrolled. Radiotherapy technique included intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). Through a propensity score matched (PSM) method, 71 patients receiving IC and CCRT were matched 1:1 to patients who received CCRT alone, according to age, gender, performance status, tumor length, and pre-treatment TN stage. The Kaplan-Meier method and Cox proportional hazards model were applied to analyze survival and prognosis. The IC + CCRT group had no improvement in 5-year overall survival (OS) rate (39.0% vs 29.3%, p = 0.360), recurrence-free survival (RFS) rate (39.0% vs 26.9%, p = 0.142), and distant metastasis-free survival (DMFS) rate (33.6% vs 27.2%, p = 0.515) compared with the CCRT group. The overall clinical response rate was 45.1% after IC in the IC + CCRT group. The IC responders (CR + PR + SD) group showed more favorable 5-year OS (41.7% vs. 14.3% vs. 29.3%, p < 0.001), RFS (41.7% vs. 14.3% vs. 26.9%, p < 0.001) and DMFS (37.3% vs. 0% vs. 27.2%, p < 0.001) compared with the IC non-responders (PD) group and the CCRT group. Besides, the 5-year OS rate (65.6% vs. 17.6% vs. 29.3%, p < 0.001), RFS rate (65.6% vs. 17.6% vs. 26.9%, p < 0.001), and DMFS rate (62.5% vs. 10.3% vs. 27.2%, p < 0.001) of the IC good responders (CR + PR) were significantly higher than that of the IC poor responders (SD + PD) and CCRT group. Multivariate analysis revealed that total radiotherapy time (≥ 49 days) and AJCC stage (Ⅲ/Ⅳ) were independent predictive factors of OS, RFS and DMFS. Besides, age was an independent predictive factor of DMFS. No significant difference was observed in the rates of grades 3-4 toxicities between both groups. Our results showed the addition of IC to CCRT was not superior to CCRT in unselected ESCC patients, while IC responders could benefit from this regime without increase in toxicities.

A Pilot Study of Stereotactic Body Radiotherapy and 177Lu-PSMA-617 for Oligometastatic Hormone Sensitive Prostate Cancer

Stereotactic body radiotherapy (SBRT) is increasingly used for oligorecurrent prostate cancer (OPC). Despite excellent local control, distant metastasis free survival rates are more modest. We hypothesized SBRT outcomes could be optimized with improved staging imaging and integration of a well-tolerated targeted radiopharmaceutical therapy (RLT) for microscopic disease. We report initial results of a prospective, single-institution pilot (NCT05079698) of a novel, PSMA-based theranostic strategy for OPC. Men with castrate sensitive OPC and 1-3 sites of PSMA PET avid disease ("index lesions") and no PSMA non-avid sites were eligible. No androgen deprivation therapy was permitted. Subjects first received 2 cycles of 177Lu-PSMA-617 RLT (7.47±0.14 GBq) spaced 6 weeks apart. In vivo dosimetry was performed during cycle 1. Four weeks post-cycle 2, patients were restaged with 68Ga-PSMA PET for an interim (post-RLT) response assessment. Index lesions were then consolidated with SBRT (9 Gy x 3) irrespective of post-RLT PET response. The primary outcome was feasibility defined as successful completion of protocol-mandated therapy without intercurrent distant failure on post-RLT PET. Six men were treated with nine total index lesions (5 nodal, 3 osseous, 1 visceral). The study met its primary endpoint; all completed required interventions and no distant progression was seen on interim PSMA PET. Treatment was well tolerated; no grade 3+ toxicities, 2/6 had grade 2 toxicities (transient anemia and hyperbilirubinemia) and 5/6 had grade 1 toxicities. Median baseline lesion-level PSMA SUVmax was 16.8±8.7. Median interim SUVmax was 6.2±2.5 and declined for all but one lesion post-RLT (median -65%). Median SUVmax at 3-mos post-SBRT was 3.3±2.5 and decreased for all evaluable lesions (median -80%). Median baseline PSA was 2.01 ng/mL (range: 0.72-4.56) which declined in 5/6 post-RLT. The 6th patient experienced biochemical rise with interim PET showing only greater avidity in the known index lesion and SBRT was completed per protocol. All 4 evaluable patients with at least one post-SBRT follow-up have improved PSA at last visit (range 5.5-12 mos from cycle 1), and 2/4 have undetectable PSA. Composite dosimetry, correlatives and quality of life studies are forthcoming. Our pilot study demonstrates the feasibility of a novel PSMA anchored theranostic strategy combining SBRT with targeted RLT for OPC. Preliminary data suggests promising outcomes, including the possibility of achieving an undetectable biochemical disease state without hormone therapy.

Comparison of Supraclavicular Surgery plus Radiotherapy vs. Radiotherapy Alone in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis: A Multicenter Retrospective Study

To evaluate and compare the outcomes of supraclavicular lymph node dissection (SLND) plus radiotherapy (RT) and RT alone for patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM). In all, 293 patients with sISLM across three centers were included. Of these, 85 (29.0%) received SLND plus RT and 208 (71.0%) received RT alone. All patients received preoperative systemic therapy followed by mastectomy or lumpectomy and axillary dissection. Supraclavicular recurrence-free survival (SCRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated by using the Kaplan-Meier method and multivariate Cox models. Multiple imputation was used for missing data. The median follow-up duration of the RT and SLND+RT groups were 53.7 and 63.5 months, respectively. For the RT and SLND+RT groups, the 5-year SCRFS rates were 91.7% vs. 85.5% (P = 0.522), LRRFS rates were 79.1% vs. 73.1% (P = 0.412), DMFS rates were 60.4 vs. 58.8% (P = 0.708), DFS rates were 57.6% vs. 49.7% (P = 0.291), and OS rates were 71.9% vs. 62.2% (P = 0.272), respectively. There was no significant effect on any outcome when comparing SLND+RT versus RT alone in the multivariate analysis. Based on four risk factors of DFS, patients were classified into three risk groups: the intermediate- and high-risk groups had significantly lower survival outcomes than the low-risk group. SLND+RT did not improve outcomes of any risk group compared with RT alone. Patients with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups.

A Pilot Trial of Consolidation Bevacizumab after Hypo-Fractionated Concurrent Chemoradiotherapy in Patients with Unresectable Locally Advanced Non-Squamous Non-Small-Cell Lung Cancer

To assess the feasibility of adding bevacizumab consolidation into hypo-fractionated concurrent chemoradiotherapy (hypo-CCRT) in patients with unresectable locally advanced non-squamous non-small cell lung cancer (LA-NS-NSCLC). Eligible patients were treated with hypo-RT (40 Gy in 10 fractions) followed by hypo-boost (24-28 Gy in 6-7 fractions) combined with concurrent weekly chemotherapy. Patients completed the hypo-CCRT without≥G2 toxicities then received consolidation bevacizumab every 3 weeks for up to 1 year, or disease progression or unacceptable treatment related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. The secondary endpoint was progression-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS) and objective response rate (ORR). All time-to-event endpoints (OS, PFS, LRFS and DMFS) were measured from the start of radiotherapy. From December 2017 to July 2020, a total of 27 patients were analyzed with a median follow-up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Besides, there were 7 patients (25.9%) had G3 cough and 3 patients (11.1%) had G3 pneumonitis. The ORR was 92.6% of the whole cohort. The median OS was 37.0 months (95% confidence interval, 8.9-65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0-18.0 months), the median LRFS was not reached and the median DMFS was 18.0 months. This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo-CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC is warranted while G3 respiratory toxicities is worth considering.

Standard Therapy vs. Individualized Therapy in Elderly Locally Advanced Nasopharyngeal Carcinoma: A Real-World Study

Concurrent chemoradiotherapy (CRT) with/without induction chemotherapy has been the standard therapy (ST) for locally advanced nasopharyngeal carcinoma (LA-NPC). However, most patients supporting these clinical trials were younger than 65 years of age. For the toxicity of CRT and the poor tolerance of elderly patients, it is still controversial whether ST could bring the most promising survival benefits for elderly NPC compared with individualized therapy (IT). Thus, in this real-world study we compared the survival and safety of ST with IT in elderly LA-NPC to explore an effective and tolerable treatment strategy for elderly LA-NPC. A total of 109 newly diagnosed elderly LA-NPC (>65 years old) from Jan. 2013-Jul. 2020 were retrospectively enrolled and divided into the ST group and IT group according to the original treatment tendency. ST refers to CRT with/without induction chemotherapy. IT group included patients not suitable for CRT and were given individualized treatment fully discussed by at least two oncologists from our head and neck team. A 1:1 propensity score matching (PSM) generated a matched cohort of ST and IT. The survivals and treatment related toxicities were compared between the two groups. There were 46 cases in the ST group and 63 cases in the IT group. The 5-year overall survival (OS) rate, cancer-specific survival (CSS) rate, progression- free survival (PFS) rate, local recurrence-free survival (LRFS) rate and distant metastasis-free survival (DMFS) rate were 68.64%, 76.42%, 73.69%, 85.67% and 86.82%, respectively. By 1:1PSM, 35 cases in each group were matched. No significant differences of OS, CSS, PFS, LRFS and DMFS were found between ST and IT groups in the PSM-matched cohorts (P = 0.87, P = 0.79, P = 0.51, P = 0.81 and P = 0.24, respectively). Compared with patients in the ST group, cases received IT were associated with less severe acute toxicities including anemia, leucopenia, neutropenia, and thrombocytopenia. For elderly LA-NPC, IT had similar survivals while less severe toxicities compared with ST, which revolutionarily challenged the role of ST for elderly LA-NPC. In the future, more studies are need to explore a less toxic treatment modality with noninferior efficacy for elderly LA-NPC.

Dose Painting Radiotherapy Guided by Diffusion-Weighted Magnetic Resonance vs. 18F-FDG-PET/CT in Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled Clinical Trial

This phase II randomized controlled trial aimed at comparing the efficacy and toxicity of diffusion-weighted magnetic resonance imaging (DWI)-guided dose painting radiotherapy (DP-RT), FDG-PET/CT-guided DP-RT, and conventional MRI-based radiotherapy (RT) in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 330 patients with stage III-IVa NPC disease were randomly assigned in a 1:1:1 ratio to receive induction chemotherapy followed by concurrent chemoradiotherapy by DWI-guided DP-RT (group A, n = 110), FDG-PET/CT-guided DP-RT (group B, n = 110), or conventional MRI-based RT (group C, n = 110). All patients received volumetric modulated arc therapy (VMAT). In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean). In group B, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx as the SUV50%max isocontour. The doses to GTVnx-DWI in group A and GTVnx-PET in group B were escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group C, planning gross tumor volume of nasopharynx (PGTVnx) was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR2200057476). Group A and B showed significant higher complete response (CR) rates than group C (100%, 100%, and 96.4% for group A, B and C, respectively, p = 0.036). In groups A, B and C, the 1-year local recurrence-free survival (LRFS) rates were 100%, 100%, and 94.5%, respectively (p = 0.002). The 1-year disease-free survival (DFS) rates were 100%, 99.1%, and 92.7%, respectively (p = 0.001). The 1-year distant metastasis-free survival (DMFS) rates were 100%, 99.1%, and 93.6%, respectively (p = 0.004). The 1-year overall survival (OS) rates were 100%, 100%, and 95.4%, respectively (p = 0.006). Group A and B had significantly higher 1-year LRFS, DFS, DMFS, and OS than those in group C. No significant differences were observed in LRFS, DFS, DMFS and OS between group A and B. Group B (PET/CT group) had a higher incidence of grade 3-4 acute ototoxicity (3.6%) than group A (0%) and group C (0%, p = 0.036). No significant differences in other grade 3-4 acute adverse events and late toxic effects were observed among the three groups, and no patient had grade 5 toxicities. Multivariate analysis showed that dose painting (DWI-guided DP-RT and PET/CT-guided DP-RT vs conventional MRI-based RT) was associated with improved LRFS, DFS, DMFS and OS. Both DWI-guided DP-RT and PET/CT-guided DP-RT plus chemotherapy are associated with improved LRFS, DFS, DMFS and OS compared with conventional MRI-based RT among patients with locoregionally advanced NPC. DWI-guided DP-RT does not increase toxicities, but PET/CT-guided DP-RT has higher incidence of acute ototoxicity.

Radiotherapy Alone vs. Concurrent or Adjuvant Chemoradiotherapy for Nasopharyngeal Carcinoma Patients with Negative Epstein-Barr Virus DNA Post-Induction Chemotherapy

Induction chemotherapy (IC) plus concurrent chemoradiotherapy has been recommended as the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, concurrent chemotherapy was associated with increased toxicities, poor tolerance, and low completion rates. The aim of this study was to compare the efficacy and toxicity of IC+ radiotherapy (RT) and IC+ concurrent or adjuvant chemoradiotherapy (IC+CCRT/AC) in patients with negative post-IC EBV DNA. A total of 547 NPC patients with negative plasma EBV DNA post-IC were included. Patients were classified into the IC+RT group and the IC+ concurrent or adjuvant chemoradiotherapy (IC+CCRT/AC) group. Locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) were estimated and compared using the Kaplan-Meier method. Propensity-score matching (PSM) was performed to balance the variables. The median follow-up time was 37 months. The 3-year LRFS, DMFS, OS, and PFS rates for the whole group were 92.2%, 92.4%, 96.4%, and 84.4%, respectively. There was no significant difference in LRFS, DMFS, OS, and PFS between the IC+RT and the IC+CCRT/AC group both before PSM (3-year rates of 91.1% vs. 92.6%, p = 0.94; 95.6% vs. 91.5%, p = 0.08; 95.2% vs. 96.8%, p = 0.80; 85.9% vs. 84.0%, p = 0.38) and after PSM (90.7% vs. 92.7%, p = 0.77; 96.8% vs. 93.7%, p = 0.29; 94.5% vs. 93.9%, p = 0.57; 84.7% vs. 85.6%, p = 0.96). Multivariate analysis demonstrated that treatment schedule was not an independent predictor for survival rates. Patients in the IC+RT group had fewer treatment-related acute toxicities and better tolerance. IC+RT displayed similar survival outcomes as IC+CCRT/AC for NPC patients with negative post-IC EBV DNA. Our current data seems not to support the routine use of concurrent or adjuvant chemotherapy after IC for unselected patients.

Neoadjuvant chemotherapy for organ preservation in sinonasal squamous cell carcinoma.

In this study, we aimed to evaluate the role of induction chemotherapy (IC) in the treatment of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). 130 patients who accepted IC between 2010 and 2022 were retrospectively reviewed. After IC, all the patients underwent chemoradiotherapy (CRT)/ radiotherapy (RT) or CRT/RT followed by surgery. We investigated the objective response to IC, the optimal treatment strategy, organ preservation, and long-term survival. Eighty-seven patients (66.9%) achieved a partial response after IC. 86% (27/43) of the patients who did not respond to the IC still presented a sensitive response to radiotherapy (χ2 = 9.26, p = 0.005). Patients who respond to IC could benefit from CRT/RT followed by surgery over other treatment modalities. The 3-year overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of61.2%, 51.3%, 52.1%, 58.1% for the IC response group were significantly superior to those of 37.3% (HR = 0.58, 95% CI 0.34-1.01, p = 0.030), 33.5% (HR = 0.49, 95% CI 0.30-0.82, p = 0.002), 35.9% (HR = 0.54, 95% CI 0.32-0.91, p = 0.009), 36.1% (HR = 0.60, 95% CI 0.35-1.03, p = 0.040) for the IC non-response group. Patients who responded to IC had a high rate of organ preservation compared with patients who did not respond to IC (90.8% vs. 74.4%, χ2 = 6.19, p = 0.013). The results demonstrated a response rate to IC in patients with advanced SNSCC; furthermore, the response to IC indicated better survival. Patients who responded to IC had a high rate of organ preservation.

Preservation of the pectoralis major fascia has no impact on the long-term oncologic outcomes of patients with breast cancer treated with conservative mastectomy and immediate breast reconstruction: A propensity score matching analysis

The oncologic safety of preserving the pectoralis major fascia (PMF) in patients with breast cancer remains controversial. In this study, we aimed to determine the impact of preserving the PMF on long-term oncologic outcomes in patients with breast cancer treated with immediate implant-based breast reconstruction (IBBR) following conservative mastectomy. We selected women with early-stage breast cancer who underwent conservative mastectomy and submuscular IBBR in our center during 2014-2019. The propensity score matching method was used to create well-balanced fascia-preserved and fascia-removed groups. Locoregional recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the fascia-preserved and fascia-removed groups. After matching, there were 219 patients in each group. The mean follow-up time was 64.8±18.1 months for the fascia-preserved group and 64.9±18.4 months for the fascia-removed group. There were no significant differences between the groups in terms of LRFS (91.3% vs. 93.8%; p=0.818), DMFS (94.0% vs. 92.3%; p=0.056), DFS (89.9% vs. 88.4%; p=0.261), and OS (95.8% vs. 95.4%; p=0.783) rates. In the fascia-preserved group, 61.5% of the locoregional recurrence events occurred within 2 years after surgery. Preservation of the PMF did not significantly impact the long-term oncologic outcomes in patients with breast cancer who underwent conservative mastectomy and IBBR. The PMF might be safely preserved in patients without suspicious tumor invasion into this fascia.

Long-term outcomes of whole-pelvis radiation therapy using volumetric modulated arc therapy for high-risk prostate cancer†.

This study investigated the outcomes of whole-pelvis radiation therapy (WPRT) using volumetric modulated arc therapy (VMAT) for high-risk prostate cancer. We retrospectively analysed 112 patients with high-risk prostate cancer who started WPRT at our hospital between August 2011 and August 2015. The prescribed dose was 78Gy in 39 fractions to the prostate and 46.8Gy in 26 fractions to the pelvic lymph node (LN) area. All patients received long-term androgen deprivation therapy. We evaluated late gastrointestinal (GI) and genitourinary (GU) toxicities using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for censored cases was 97 (interquartile range [IQR] = 85-108) months. The median age was 72 (IQR = 67-75) years. The high-risk and very-high-risk groups included 41 (36.6%) and 71 patients (63.4%), respectively. The median risk of LN invasion calculated by the Roach formula was 36.9 (IQR = 26.6-56.3) %. The 8-year overall survival, biochemical failure-free survival, disease-free survival and distant metastasis-free survival rates were 88.4, 91.9, 83.8 and 98.0%, respectively. Only one patient experienced common iliac LN recurrence, which was outside the pelvic irradiation area. All patients with recurrent disease were categorized into the very-high-risk group. The 8-year cumulative rates of ≥Grade 2 late GI and GU toxicities were 12.8 and 11.8%, respectively. No patients experienced Grade 4 or higher toxicities. WPRT using VMAT for high-risk prostate cancer was well tolerated and effective.

Nomogram for prognosis of elderly patients with cervical cancer who receive combined radiotherapy

This retrospective study identified prognostic factors to help guide the clinical treatment of elderly patients (≥ 65 years) with cervical cancer who had undergone radiotherapy. A personalized model to predict 3- and 5-years survival was developed. A review was conducted of 367 elderly women with cervical cancer (staged II–III) who had undergone radiotherapy in our hospital between January 2012 and December 2016. The Cox proportional hazards regression model was used for survival analysis that considered age, hemoglobin, squamous cell carcinoma antigen, pathologic type, stage, pelvic lymph node metastasis status, and others. A nomogram was constructed to predict the survival rates. The median follow-up time was 71 months (4–118 months). The 3- (5-) years overall, progression-free, local recurrence-free, and distant metastasis-free survival rates were, respectively, 91.0% (84.4%), 92.3% (85.9%), 99.18% (99.01%), and 99.18% (97.82%). The following were significant independent prognostic factors for overall survival: tumor size, pre-treatment hemoglobin, chemotherapy, and pelvic lymph node metastasis. The C-index of the line chart was 0.699 (95% CI 0.652–0.746). The areas under the receiver operating characteristic curves for 3- and 5-years survival were 0.751 and 0.724. The nomogram was in good concordance with the actual survival rates. The independent prognostic factors for overall survival in elderly patients with cervical cancer after radiotherapy were: tumor size, pre-treatment hemoglobin, chemotherapy, and pelvic lymph node metastasis. The novel prognostic nomogram based on these factors showed good concordance with the actual survival rates and can be used to guide personalized clinical treatment.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

New Insights on the Importance of the Extent of Vascular Invasion in Widely Invasive Follicular Thyroid Carcinoma.

This study aimed to investigate the association between the extent of vascular invasion (VI) and the outcome of widely invasive follicular thyroid carcinoma (WI-FTC). The records of 107 patients with WI-FTC confirmed by surgical specimens from January 2005 to December 2016 were retrospectively reviewed. Among the 107 patients with WI-FTC, those with a VI of < 4 (n = 62) and ≥ 4 (n = 45) had a 10year cause-specific survival (CSS) rate of 97.7% and 89.4% (p = 0.008), respectively. Univariate analysis identified M1 (p = 0.001), and the number of VI of ≥ 4 as significant negative prognostic factors for CSS. Multivariate analysis identified M1 (hazard ratio [HR] = 9.366) as independent negative prognostic factor for CSS. Among the 72 patients with M0 WI-FTC, those with a VI of < 2 (n = 33) and ≥ 2 (n = 39) had a 10-year distant metastasis-free survival (DMFS) rate of 96.8% and 56.8% (p = 0.001), respectively. Univariate analysis identified age ≥ 55years (p = 0.011), presence of VI, the number of VI of ≥ 2, and resection margin status (p < 0.001) as significant negative prognostic factors for DMFS. Multivariate analysis identified the number of VI ≥ 2 (HR = 9.137), and resection margin status (HR = 5.853) as independent negative prognostic factors for DMFS. It may be unnecessary that WI-FTC with curative resection margin status and a VI of < 2, especially in capsular invasion only, routinely undergo completion thyroidectomy and postoperative ablation.

Clinical characteristics, prognostic factors, and treatment modalities for head and neck lymphoepithelioma-like carcinoma: A real-world study from southern China

BackgroundWe aimed to elucidate the clinical characteristics, prognostic factors and optimal treatment modalities of head and neck lymphoepithelioma-like carcinoma (HNLELC). MethodsConsecutive patients newly-diagnosed with non-metastatic HNLELC between December 2001 and March 2021 treated with curative intent were retrospectively reviewed. ResultsA total of 288 patients were included, of whom 87 (30.2%) underwent radical surgery alone, 43 (14.9%) underwent definitive radiotherapy with or without concurrent chemotherapy, and 158 (54.9%) underwent surgery followed by postoperative radiotherapy (SRT). Epstein-Barr virus-encoded small RNA (EBER) was positive in 94.8% (239/252) of patients. Cervical node infiltration was seen in 52.8% (152/288) of patients. No significant difference was found in nodal metastasis rate between T1–2 and T3–4 classifications (49.5% vs. 56.5%, p = 0.308). The 3-year overall survival (OS), disease-free survival, locoregional relapse-free survival, and distant metastasis-free survival rates were 89.4%, 78.7%, 89.2%, and 87.7%, respectively. Compared to SRT, surgery alone associated with significant reduced 3-year local (92.8% vs. 96.5%, p = 0.012) and regional relapse-free survival rates (89.3% vs. 96.8%, p = 0.002). Definitive radiotherapy and SRT demonstrated comparable results in all 3-year survival outcomes (all p＞0.05). Multivariate analysis found EBER status was an independent favorable prognostic factor for OS (HR = 0.356, 95% CI: 0.144–0.882, p = 0.026). ConclusionHNLELC was observed to associate with EBV infection and cervical nodal infiltration. Definitive radiotherapy achieved similar survival outcomes compared to SRT, and may serve as a good substitute for patients unfit or unwilling to undergo surgery.

The Role of Parotid Gland Invasion in Adenoid Cystic Carcinoma of the External Auditory Canal.

This study aimed to investigate the significance of parotid gland invasion in predicting distant metastasis of adenoid cystic carcinoma in the external auditory canal. Single-institution retrospective cohort study. A retrospective review of patients with adenoid cystic carcinoma of the external auditory canal who underwent surgery was performed. Information on patient demographics, parotid gland invasion, tumor stage, perineural invasion, lymphovascular invasion, and follow-up data were collected and analyzed. One hundred twenty-nine patients were identified for review. Parotid gland invasion was noted in 45 patients (34.9%). Parotid gland invasion was significantly associated with tumor stage, perineural invasion, distant metastasis, and postoperative adjuvant therapy. Distant metastasis was noted in 30 patients (23.3%). Multivariate Cox proportional hazards analysis identified parotid gland invasion as an independent risk factor for predicting distant metastasis. The 5-year distant metastasis-free survival rate was 83.6% for patients without parotid gland invasion and 61.8% for patients with parotid gland invasion (p = 0.010). The parotid gland invasion rate is relatively high in adenoid cystic carcinoma of the external auditory canal and is significantly related to tumor stage. Parotid gland invasion is associated with worse distant metastasis-free survival. 4 Laryngoscope, 134:419-425, 2024.

Simultaneous integrated or sequential boost to clinically involved lymph nodes in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy

ObjectiveThe optimal treatment of metastatic lymph nodes (LNs) in locally-advanced cervical cancer (LACC) is controversial. With the widespread use of modern radiotherapy (RT) techniques, it is become possible to perform dose escalation in clinically involved LNs. This study aimed to evaluate the oncologic outcomes of dose escalation to the involved LNs with the simultaneous-integrated (SIB) or sequential boost (SEB) techniques as a part of definitive chemoradiotherapy (CRT) for patients with LACC. MethodsThe data of 47 patients treated with definitive CRT with either a SIB or SEB technique to the metastatic LNs between 2015 and 2021 were retrospectively analyzed. All patients received 50.4 Gy/28 fractions of external-beam RT and 28 Gy/4 fractions of brachytherapy. ResultsThe number of boosted LNs was 146. The median size of the LNs was 2 cm (range, 1–5 cm). The median cumulative equivalent dose in 2-Gy fractions for the LNs was 64.2 Gy (range, 57.6–71.2 Gy). During the median 30 months of follow-up (range, 14–91 months), no boosted LNs recurred and the local control (LC) rate was 100%. The 2-year overall, disease-free, local recurrence-free, and distant metastasis-free survival rate was 83.1%, 70.5%, 77.5%, and 74.4%, respectively. In multivariate analysis, the non-squamous cell histology was the only negative independent prognostic factor for DFS and DMFS. Treatment was well tolerated without any serious acute toxicity. Serious late toxicity developed in three (6%) patients as ureteral stenosis, rectal bleeding and pelvic fracture in one patient each. ConclusionsRT dose escalation provides excellent LC for the clinically involved LNs, even for bulky ones, with a low toxicity profile. Routine LN dissection may not be necessary. However, randomized trials are needed to determine the optimal treatment approach.

“Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study”

BackgroundPathologic complete response (pCR) after multimodal treatment for locally advanced rectal cancer (LARC) is used as surrogate marker of success as it is assumed to correlate with improved oncologic outcome. However, long-term oncologic data are scarce. MethodsThis retrospective, multicentre study updated the oncologic follow-up of prospectively collected data from the Spanish Rectal Cancer Project database. pCR was described as no evidence of tumour cells in the specimen. Endpoints were distant metastases-free survival (DMFS) and overall survival (OS). Multivariate regression analyses were run to identify factors associated with survival. ResultsOverall, 32 different hospitals were involved, providing data on 815 patients with pCR. At a median follow-up of 73.4 (IQR 57.7–99.5) months, distant metastases occurred in 6.4% of patients. Abdominoperineal excision (APE) (HR 2.2, 95%CI 1.2–4.1, p = 0.008) and elevated CEA levels (HR = 1.9, 95% CI 1.0–3.7, p = 0.049) were independent risk factors for distant recurrence. Age (years) (HR 1.1; 95%-CI 1.05–41.09; p < 0.001) and ASA III-IV (HR = 2.0; 95%-CI 1.4–2.9; p < 0.001), were the only factors associated with OS. The estimated 12, 36 and 60-months DMFS rates were 96.9%, 91.3%, and 86.8%. The estimated 12, 36 and 60-months OS rates were 99.1%, 94.9% and 89.3%. ConclusionsThe incidence of metachronous distant metastases is low after pCR, with high rates of both DMFS and OS. The oncologic prognosis in LARC patients that achieve pCR after neoadjuvant chemo-radiotherapy is excellent in the long term.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial

The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC+CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P=.045) and symptoms including dry mouth (P=.004), sticky saliva (P=.047), and feeling ill (P=.041). After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

Pembrolizumab versus placebo as adjuvant therapy in stage IIB or IIC melanoma: Final analysis of distant metastasis-free survival in the phase 3 KEYNOTE-716 study.

LBA9505 Background: Adjuvant pembrolizumab significantly improved distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) in patients with resected stage IIB or IIC melanoma versus placebo. We present the protocol-specified final DMFS analysis from KEYNOTE-716 (NCT03553836). Methods: Eligible patients were ≥12 years old with resected stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer, 8th edition, guidelines and a negative sentinel lymph node biopsy. In part 1 of the study, patients were randomly assigned (1:1) to pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for up to 17 cycles (~1 year) or until disease recurrence, unacceptable toxicity, or withdrawal. Randomization was stratified by T category for adults (T3b vs T4a vs T4b), with a separate stratum for pediatric patients. The primary end point was RFS per investigator review. DMFS per investigator review was a secondary end point. The protocol-specified final DMFS analysis was based on a target of 195 DMFS events. No formal hypothesis testing was performed because DMFS and RFS end points were met at previous interim analyses. The data cutoff date for this analysis was January 4, 2023. Results: Overall, 976 patients were randomly assigned to receive pembrolizumab (n = 487) or placebo (n = 489). Median duration of follow-up (time from randomization to the data cutoff date) was 39.4 months (range, 26.0-51.4). Compared with placebo, adjuvant pembrolizumab improved DMFS (medians: not reached; hazard ratio [HR], 0.59 [95% CI, 0.44-0.79]) and RFS (medians: not reached; HR, 0.62 [95% CI, 0.49-0.79]). The 36-month DMFS rate was 84.4% with adjuvant pembrolizumab versus 74.7% with placebo; the 36-month RFS rate was 76.2% with adjuvant pembrolizumab versus 63.4% with placebo. DMFS benefit with adjuvant pembrolizumab over placebo was observed regardless of cancer stage at baseline (stage IIB HR, 0.62 [95% CI, 0.42-0.92]; stage IIC HR, 0.57 [0.36-0.88]). Similar results were observed with RFS (stage IIB HR, 0.58 [95% CI, 0.43-0.79]; stage IIC HR, 0.65 [95% CI, 0.45-0.94]). No new safety signals were observed. Conclusions: With a median follow-up of 39.4 months, adjuvant pembrolizumab for resected stage IIB and IIC melanoma continued to show DMFS and RFS benefit over placebo, with no new safety signals. Clinical trial information: NCT03553836 .