Increase of prostate-specific antigen doubling time predicts survival in metastatic castration-resistant prostate cancer patients undergoing radium therapy.

OBJECTIVE: Radium-223 (Ra-223) is an important treatment modality for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). However, there is currently a lack of effective markers to monitor treatment response during treatment. We aim to investigate the response in prostate-specific antigen doubling time (PSADT) as a potential marker for assessing Ra-223 treatment in mCRPC patients. METHODS: We retrospectively collected data from mCRPC patients who underwent radium treatment at our institution between August 2020 and June 2023. Prostate-specific antigen (PSA) measurements prior to treatment and during treatment were collected. Baseline PSADT was calculated from PSA measurements prior to Ra-223 treatment; interim PSADT was calculated from PSA measurements before Ra-223 treatment and prior to the fourth course injection. Overall survival was calculated from the start of treatment to the date of death. Univariable and multivariable analysis using the Cox proportional hazards model were performed to examine the association of factors with overall survival. RESULTS: We included 35 patients from our institution, with a median overall survival of 13.3 months. Eighteen (51.4%) completed all six courses of treatment. PSA dynamic response (interim PSADT > baseline PSADT or decreased PSA) was observed in 20 patients. Overall survival was associated with a PSA dynamic response (HR = 0.318, 95% CI 0.133-0.762, p = 0.010) when compared to patients without response. CONCLUSIONS: Dynamic changes in PSADT were associated with survival in mCRPC patients receiving radium therapy. Comparing interim and baseline PSADT could serve as a valuable marker for determining treatment benefits.

The role of postoperative radiotherapy or chemoradiation in pT1-2N1M0 oral squamous cell carcinoma.

BACKGROUND: Postoperative radiotherapy (PORT) and concurrent chemoradiation (CCRT) are indicated for patients with advanced oral cancer. However, the benefits for pT1-2N1 disease without adverse pathological features are controversial. METHODS: This retrospective study using the Taiwan Cancer Registry database included patients with pT1-2N1 oral cancer from January 1, 2011, to December 31, 2017. Overall survival was analyzed in patients receiving surgery alone, PORT, or CCRT. RESULTS: Among the 862 patients, the five-year overall survival rate in patients receiving surgery alone, PORT, and CCRT was 62.2%, 58.7%, and 71.1% (P = 0.03), respectively. CCRT was associated with longer survival than PORT (P = 0.008). Survival in patients with pT2 disease was significantly higher with CCRT than PORT (P = 0.001), but no difference was observed in pT1 disease. CONCLUSION: CCRT demonstrated a favorable impact on survival outcomes in patients diagnosed with pT2N1 oral cancer when compared to PORT. However, no significant survival benefits were observed for patients with pT1 disease.

Entrapment neuropathy of common peroneal nerve by fabella: A case report.

BACKGROUND: Neuropathy of the common peroneal nerve caused by compression by a fabella is an extremely rare form of compression neuropathy. Involving both the superficial and deep peroneal nerves, it usually manifests as either impaired sensation from the lower lateral leg to the top of the foot or drop foot, or as a combination of both. CASE SUMMARY: We report the case of a 58-year-old Asian female who presented with inversion of the right foot during the stance phase of gait without sensory complaints related to the lower leg. Electrodiagnostic testing revealed the neuropathy of the common peroneal nerve at the level of the knee, exclusively affecting the muscular branch of the superficial peroneal nerve. A neuromuscular ultrasound disclosed swelling of the right common peroneal nerve just before it crossed over a large fabella as well as atrophy and fatty infiltration of the right peroneus longus and peroneus brevis muscles. Surgical excision of the fabella and neurolysis were performed. Subsequently, the strength of the right foot evertors improved, but the unsteady gait with occasional falls persisted for nine months after the surgery. Therefore, another procedure was performed to transfer the split posterior tibialis tendon to the peroneus brevis in order to correct the gait. CONCLUSION: This is the first case of neuropathy of the common peroneal nerve caused by compression by a fabella affecting exclusively the muscular branch of the superficial peroneal nerve. Clinicians should be aware of this unusual peripheral neuropathy while evaluating and treating patients with gait disturbance.

Development and validation of a machine learning model of radiation-induced hypothyroidism with clinical and dose-volume features.

BACKGROUND AND PURPOSE: Radiation-induced hypothyroidism (RIHT) is a common but underestimated late effect in head and neck cancers. However, no consensus exists regarding risk prediction or dose constraints in RIHT. We aimed to develop a machine learning model for the accurate risk prediction of RIHT based on clinical and dose-volume features and to evaluate its performance internally and externally. MATERIALS AND METHODS: We retrospectively searched two institutions for patients aged >20 years treated with definitive radiotherapy for nasopharyngeal or oropharyngeal cancer, and extracted their clinical information and dose-volume features. One was designated the developmental cohort, the other as the external validation cohort. We compared the performances of machine learning models with those of published normal tissue complication probability (NTCP) models. RESULTS: The developmental and external validation cohorts consisted of 378 and 49 patients, respectively. The estimated cumulative incidence rates of grade ≥1 hypothyroidism were 53.5% and 61.3% in the developmental and external validation cohorts, respectively. Machine learning models outperformed traditional NTCP models by having lower Brier scores at every time point and a lower integrated Brier score, while demonstrating a comparable calibration index and mean area under the curve. Even simplified machine learning models using only thyroid features performed better than did traditional NTCP algorithms. The machine learning models showed consistent performance between folds. The performance in a previously unseen external validation cohort was comparable to that of the cross-validation. CONCLUSIONS: Our model outperformed traditional NTCP models, with additional capabilities of predicting the RIHT risk at individual time points. A simplified model using only thyroid dose-volume features still outperforms traditional NTCP models and can be incorporated into future treatment planning systems for biological optimization.

Recurrent spinal meningeal melanocytoma at lumbar spine level: a case report.

INTRODUCTION: Spinal meningeal melanocytoma is an extremely rare tumour with an estimated annual incidence of 1 per 10 million people. It usually arises from the intradural extramedullary compartment at the cervical levels. Although these tumours are histologically benign, they may behave aggressively. Local recurrence could occur even after total tumour excision. CASE REPORT: We report a case of a 33-year-old Asian male who developed progressive weakness and numbness of the bilateral lower extremities as well as urinary retention five years after complete tumour resection of lumbar spinal meningeal melanocytoma. Magnetic resonance imaging of the lumbar spine revealed a mass with thecal sac compression which was hypointense on T2-weighted images and hyperintense on T1-weighted images. The patient underwent total tumour removal. Histologic examination was compatible with recurrent meningeal melanocytoma. After a 4-week inpatient rehabilitation programme, he was able to ambulate without assistance and to do clean intermittent catheterisation for micturition on a regular basis. DISCUSSION: This is the first reported case of intradural extramedullary meningeal melanocytoma located at the lumbar region. Clinicians should consider the possibility of these rare tumours at any level of the spine, and be aware of sphincter dysfunction in addition to motor and sensory deficits of extremities.

Early post-treatment 18F-FDG PET/CT for predicting radiation-induced hypothyroidism in head and neck cancer.

BACKGROUND: Radiation-induced hypothyroidism (RIHT) is a common, but underestimated, late adverse effect in head and neck cancer. We investigated the value of early post-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting RIHT. METHODS: We searched our institutional database for patients aged ≥ 20 years who had undergone definitive radiotherapy for nasopharyngeal or oropharyngeal cancer between 2005 and 2017, followed by 18F-FDG PET/CT within 180 days of radiotherapy completion. We visually assessed and compared PET/CT and baseline characteristics in patients with and without RIHT using the chi-square test for categorical variables and the t-test for continuous variables. Variable predictive ability was evaluated by measuring the area under receiver operating characteristic curves. RESULTS: Fifty-two patients were included; 22 (42%) developed RIHT and 30 (58%) did not. Two patients presented with diffuse thyroid uptake on PET/CT via visual assessment, and both developed RIHT later. Among the PET/CT variables, thyroid functioning volume was significantly higher in patients without RIHT than in patients with RIHT (16.30 ± 6.03 cm3 vs. 10.61 ± 3.81 cm3, p < 0.001). The maximum standard uptake values of the thyroid and pituitary glands did not differ significantly between the groups. Two patient characteristics, pretreatment thyroid volume and mean radiotherapy dose to the thyroid, also showed significant differences between the groups. An algorithmic approach combining visual grading of thyroid 18F-FDG uptake and thyroid functioning volume cutoff of 14.01 yielded an area under curve of 0.89 (95% confidence interval, 0.80-0.98); the sensitivity, specificity, positive predictive value, and negative predictive value were 87.0%, 82.3%, 80.0%, and 88.9%, respectively. CONCLUSION: Early post-treatment PET/CT-derived thyroid functioning volume was a good predictor of RIHT development. Diffusely increased thyroid 18F-FDG uptake on PET/CT may indicate impending RIHT. Routine surveillance of thyroid function is warranted in patients at high risk of developing RIHT.

Contralateral Neck Irradiation Can Be Omitted for Selected Lateralized Oral Cancer in Locally Advanced Stage.

(1) Background: To investigate the contralateral neck failure (cRF) rates and outcomes among patients with well-lateralized locally advanced oral cavity squamous cell carcinoma (OSCC) with/without ipsilateral or bilateral neck adjuvant irradiation. (2) Methods: Patients with lateralized OSCC diagnosed between 2007 and 2017 were retrospectively enrolled. Patients who had undergone curative surgery with pathologically proven pT3/4 or pN0-2b without distant metastasis were included, while those with cross-midline, neck-level 1a involvement and positive extra-nodal extension (ENE) were excluded. The primary endpoint was the cumulative incidence of 5-year cRF as the first site of failure. The secondary endpoints included cancer-specific survival (CSS), local-regional recurrence-free survival (LRRFS), distant-metastasis-free survival (DMFS), and contralateral-regional recurrence-free survival (cRRFS). (3) Results: In total, 149 patients were analyzed with a median follow-up time of 5.2 years (range, 2.91-7.83). Pathological stages T3 and T4 were 22.7% and 56.8%, respectively. Pathologically negative and positive lymph nodes were 61.4% and 38.6%, respectively. The cumulative 5-year cRF rate was 3.6% (95% CI, 1.3-7.7%). No significant differences in the 5-year CSS, LRRFS, DMFS, and cRRFS were observed among those undergoing unilateral or bilateral neck irradiation. Five patients (3.4%) had contralateral neck recurrence, all simultaneously with local recurrence. No isolated contralateral neck recurrence was identified. (4) Conclusions: The cRF rate was acceptably low in patients with well-lateralized advanced OSCC with the initially uninvolved contralateral neck. Omitting contralateral neck irradiation with active surveillance could be considered without compromising the cure rate in locally advanced OSCC patients.

Improved overall survival is associated with adjuvant chemotherapy after definitive concurrent chemoradiotherapy for N3 nasopharyngeal cancer.

Concurrent chemoradiotherapy is the established treatment for locally advanced nasopharyngeal carcinoma (NPC). However, there is no evidence supporting routine adjuvant chemotherapy. We aimed to demonstrate the effect of adjuvant chemotherapy on survival and distant metastasis in high-risk N3 NPC patients. We linked the Taiwan Cancer Registry and Cause of Death database to obtain data. Clinical N3 NPC patients were divided as those receiving definitive concurrent chemoradiotherapy (CCRT) with adjuvant 5-fluorouracil and platinum (PF) chemotherapy and those receiving no chemotherapy after CCRT. Patients receiving neoadjuvant chemotherapy were excluded. We compared overall survival, disease-free survival, local control, and distant metastasis in both groups using Cox proportional hazards regression analysis. Propensity-score matching was also performed to evaluate the independent effect of adjuvant PF in a matched cohort with similar baseline characteristics. We included 431 patients (152 and 279 patients in the adjuvant PF and observation groups, respectively). Median follow-up was 4.3 years. The 5-year overall survival were 69.1% and 57.4% in the adjuvant PF chemotherapy and observation groups, respectively (p = 0.02). Adjuvant PF chemotherapy was associated with a lower risk of death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43-0.84; p = 0.003), even after adjusting for baseline prognostic factors (HR 0.61, 95% CI 0.43-0.86; p = 0.005). Distant metastasis-free survival at 12 months was higher in the adjuvant PF chemotherapy group than in the observation group (98% vs 84.8%; p < 0.001). After adjusting for baseline prognostic factors, adjuvant PF chemotherapy was associated with freedom from distant metastasis (HR 0.11, 95% CI 0.02-0.46; p = 0.003). Adjuvant chemotherapy was also associated with a decreased risk of death (HR 0.59, 95% CI 0.41-0.85, p = 0.004) in a propensity score-matched cohort. Prospective evaluation of adjuvant PF chemotherapy in N3 NPC patients treated with definitive CCRT is warranted because adjuvant PF chemotherapy was associated with improved overall survival and decreased risk of distant metastasis.

Anaplastic Thyroid Cancer Successfully Treated With Radiation and Immunotherapy: A Case Report.

OBJECTIVE: Anaplastic thyroid cancer (ATC) is a rare thyroid cancer subtype with a devastating prognosis. Novel treatment strategies are under investigation to improve the survival of patients with ATC. METHODS: We present a case of recurrent ATC treated with a combination of radiation therapy (RT) and pembrolizumab, a programmed death-1 inhibitor, with a durable complete response. RESULTS: A 63-year-old woman underwent total thyroidectomy and left neck lymph node dissection and was diagnosed with papillary carcinoma in December, 2017. She received radioiodine in April, 2018. However, a left neck mass was noted in April, 2018 with biopsy demonstrating ATC with 95% positivity for programmed death-ligand 1 immunostaining. Positron emission tomography showed fluorodeoxyglucose uptake in the left thyroid bed and multiple lymph nodes in the left retropharyngeal, left neck, and right upper paratracheal areas. Hypofractionated RT for the recurrent areas was initiated in August,2018, and concomitant pembrolizumab was given 2 days after RT. A total of 10 cycles of pembrolizumab (2 mg/kg) were given every 3 weeks. The computed tomography scan after completion of RT and 3 cycles of pembrolizumab showed shrinkage of the neck lymph nodes. The serial follow-up computed tomography scans showed further shrinkage of the lymph nodes, and there was no recurrence of ATC as of October, 2020. CONCLUSION: We describe an ATC case successfully treated with a combination of RT and pembrolizumab with a durable response of 26 months and acceptable toxicities. This result warrants further investigation of this combination regimen in the treatment of ATC.

Association of Primary Treatment Modality for Advanced-Stage Oropharyngeal Squamous Cell Carcinoma With Survival Outcomes.

Importance: Definitive chemoradiotherapy and upfront surgical treatment are both accepted as the standard of care for advanced-stage oropharyngeal squamous cell carcinoma. However, the optimal primary treatment modality remains unclear. Objective: To evaluate the comparative effectiveness of definitive chemoradiotherapy and upfront surgical treatment for advanced-stage oropharyngeal cancer. Design, Setting, and Participants: This retrospective comparative effectiveness analysis used data from the population-based Taiwan Cancer Registry. Included patients were diagnosed with clinical stage III or IV oropharyngeal squamous cell carcinoma from 2007 to 2015 and were identified from the registry. Patients with T4b or N3 disease were excluded. Data were analyzed from June 2019 through December 2020. Interventions: Definitive chemoradiotherapy or upfront surgical treatment. Main Outcomes and Measures: The primary outcome was overall survival, for which data were available through December 31, 2018. Secondary outcomes were progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival. Results: Among 1180 patients, 694 patients (58.8%) were in the definitive chemoradiotherapy group and 486 patients (41.2%) were in the upfront surgical treatment group. The median (interquartile range) follow-up was 3.62 (1.63-5.47) years, and most patients were men (1052 [89.1%] men) with a primary tumor in the tonsils (712 patients [60.3%]), moderately differentiated histology (604 patients [51.2%]), clinical N2 disease (858 patients [72.7%]), and clinical stage IVA disease (938 patients [79.5%]). The mean (SD) age was 54.59 (10.35) years. Primary treatment with an upfront surgical procedure was associated with a decreased risk of death during the study period (hazard ratio [HR], 0.81; 95% CI, 0.69-0.97; P = .02). However, when adjusted for age, subsite, histological grade, and T and N classification, upfront surgical treatment was no longer associated with an increased risk of death during the study period (HR, 0.96; 95% CI, 0.80-1.16; P = .70). Progression-free survival was worse in the group receiving upfront surgical treatment than in the group receiving chemoradiotherapy (HR, 1.64; 95% CI, 1.09-2.46; P = .02), and this difference persisted after adjusting for other factors associated with prognosis (ie, age, tumor subsite, histological grade, and T and N classification) (HR, 1.72; 95% CI, 1.12-2.66; P = .01). Conclusions and Relevance: This study found that definitive chemoradiotherapy was associated with effectiveness that was comparable with that of upfront surgical treatment when adjusted for baseline factors associated with prognosis. These findings suggest that definitive chemoradiotherapy should be considered to avoid accumulating toxic effects associated with surgical treatment and chemoradiotherapy.

Recommendations for postoperative radiotherapy in head & neck squamous cell carcinoma in the presence of flaps: A GORTEC internationally-reviewed HNCIG-endorsed consensus.

INTRODUCTION: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. MATERIAL AND METHODS: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. RESULTS: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. CONCLUSION: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.

Prognostic Significance of Pretreatment Staging With 18F-FDG PET in Esophageal Cancer: A Nationwide Population-Based Study.

PURPOSE OF THE REPORT: Without the routine use of 18F-FDG PET for initial staging of esophageal cancer, it may lead to inaccurate staging and suboptimal treatment. The purpose of this study was to evaluate the prognostic significance of pretreatment 18F-FDG PET in nonmetastatic esophageal cancer by comparing the survival between patients with and without pretreatment PET. MATERIALS AND METHODS: We selected newly diagnosed esophageal cancer patients without metastasis between 2009 and 2015 from Taiwan Cancer Registry and National Health Insurance Research Database. Pretreatment 18F-FDG PET staging was determined according to the implementation of PET within 90 days before starting treatment. Overall survival was calculated from the day of treatment initiation to the death from any cause. Survival curves were compared between patients with and without PET staging using the log-rank test. RESULTS: Of the 9078 patients included, 1765 (19.4%) and 7313 (80.6%) patients were staged with and without pretreatment PET, respectively. The median follow-up time for all patients and survivors was 1.29 years and 5.46 years, respectively. The pretreatment PET group had a lower risk of death than the no pretreatment PET group (hazards ratio, 0.74; 95% confidence interval, 0.70-0.79; P < 0.001). After adjusting for age, stage, histology, and tumor location, pretreatment PET remained significantly correlated with a lower risk of death (hazards ratio, 0.78; 95% confidence interval, 0.73-0.83; P < 0.001). CONCLUSIONS: The utilization of pretreatment 18F-FDG PET for staging in nonmetastatic esophageal malignancy is associated with a lower risk of death even after adjusting for age, stage, histology, and tumor location.

Lymph Node Number Predicts the Efficacy of Adjuvant Chemoradiotherapy in Node-Positive Endometrial Cancer Patients.

This study aimed to evaluate the value of lymph node (LN) number as a predictor for adjuvant treatment in node-positive endometrial cancer. Data of 441 patients diagnosed with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrial cancer and who underwent adjuvant chemotherapy alone or chemoradiotherapy between 2009 and 2015 from the Taiwan Cancer Registry were reviewed. The patients were stratified based on the number of positive LN as follows: 1, 2-5, and ≥ 6. The overall survival (OS) was analysed using the Kaplan-Meier method and the Cox proportional hazards model. In multivariable analysis, chemoradiotherapy was independently associated with improved OS (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.43-0.90; p = 0.01) compared with chemotherapy alone. Patients with ≥ 6 positive LNs were associated with a worse OS (HR: 2.22, 95% CI: 1.25-3.95; p = 0.006) and those with 2-5 LNs were not associated with a worse OS (HR: 1.56, 95% CI: 0.94-2.59; p = 0.09) compared to patients with one LN. When stratified based on LN number, chemoradiotherapy was found to significantly improve the 5-year OS of patients with ≥ 6 positive LNs compared to chemotherapy alone (35.9% vs. 70.0%, p < 0.001). No significant differences between chemotherapy alone and chemoradiotherapy were observed in 5-year OS among patients with one LN (73.1% vs. 80.8%, p = 0.31) or 2-5 positive LNs (71.4% vs. 75.7%, p = 0.68). Lymph node number may be used to identify node-positive endometrial cancer patients who are likely to have improved OS with intensification of adjuvant therapy.

The Role of Pretreatment Serum Neutrophil-to-Lymphocyte Ratio in Hypopharyngeal Cancer Treated with Definitive Chemoradiotherapy: A Pilot Study.

Serum neutrophil-to-lymphocytes ratio (NLR) is a potential predictive and prognostic marker in head and neck cancers. This study aimed to determine the role of pretreatment serum NLR in patients with hypopharyngeal cancer (HPC) treated with definitive chemoradiotherapy. We retrospectively investigated the correlation between clinicopathological parameters and NLR status and analysed its impact on therapeutic response and survival. A total of 120 patients treated at a single institution between 2009 and 2015 were included. The median follow-up time was 24.1 months. High NLR (NLR ≥ 4) was associated with advanced T classification (p = 0.01*) and advanced stage (p = 0.02*) based on chi-square test. We also found that high pretreatment NLR was correlated with poor treatment response (HR = 2.42, 95% CI: 1.08-5.44, p = 0.03*). Pretreatment NLR was also an independent prognostic factor for progression-free survival (HR = 1.71, 95% CI: 1.01-2.90, p = 0.046*) and overall survival (HR = 1.99, 95% CI: 1.21-3.28, p = 0.01*) while correcting for known prognostic factors. Overall, these findings support that NLR is a potential biomarker for host response to tumour aggressiveness, therapeutic response to chemoradiotherapy and survival in HPC patients. This study is limited by its retrospective nature and further validation is warranted.

Adjuvant radiotherapy after curative surgery for oral cavity squamous cell carcinoma and treatment effect of timing and duration on outcome-A Taiwan Cancer Registry national database analysis.

Conduct an accurate risk assessment of resected oral cavity squamous cell carcinoma (OSCC) patients by accessing a nationwide systemic investigation is pivotal to improve treatment outcomes. In this article, we tried to determine the impact of different prognostic factors for OSCC patients who received adjuvant radiotherapy (RT) after curative surgery, using Taiwan's national cancer registry database (TCR). A nationwide, large population-based study was conducted using TCR with patients identified from 2007 to 2015. The study variables included age, gender, cancer subsites, stage, histology grade, margin and extra-nodal extension (ENE) status, treatment type, surgery to RT interval (ORI), total RT treatment time (RTT), and RT dose. Univariate and multivariate analysis were performed to identify predictors of the variables associated with overall survival (OS), cause-specific survival (CSS), local-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). 8986 OSCC patients treated with surgery and adjuvant RT were analyzed. In multivariate analysis, worse outcomes were associated with males, older age, subsite in the oral tongue, advanced stage, higher histologic grade, involved margin, and positive ENE. ORI only showed an adverse trend in LRFS, when exceeding 7 weeks (P = .06). RTT >8 weeks was a significant poor predictor in OS, CSS and LRFS (P < .001). Extreme RT dose (>70 Gy or ≤50 Gy) also demonstrated an adverse impact on the outcomes. Prolonged RT treatment time and extreme RT doses were identified as significantly poor prognostic predictors in OSCC patients who received adjuvant RT after curative surgery.

Development and Validation of a Nomogram for Assessing Survival in Patients With Metastatic Lung Cancer Referred for Radiotherapy for Bone Metastases.

Importance: A survival prediction model for patients with bone metastases arising from lung cancer would be highly valuable. Objective: To develop and validate a nomogram for assessing the survival probability of patients with metastatic lung cancer receiving radiotherapy for osseous metastases. Design, Setting, Participants: In this prognostic study, the putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression analysis with backward elimination and model selection based on the Akaike information criterion. The nomogram was subjected to internal (bootstrap) and external validation; its calibration and discriminative ability were evaluated with calibration plots and the Uno C statistic, respectively. The training and validation set cohorts were from a tertiary medical center in northern Taiwan and a tertiary institution in southern Taiwan, respectively. The training set comprised 477 patients with metastatic lung cancer who received radiotherapy for osseous metastases between January 2000 and December 2013. The validation set comprised 235 similar patients treated between January 2011 and December 2017. Data analysis was conducted May 2018 to July 2018. Main Outcomes and Measures: The nomogram end points were death within 3, 6, and 12 months. Results: Of 477 patients in the training set, 292 patients (61.2%) were male, and the mean (SD) age was 62.86 (11.66) years. Of 235 patients in the validating set, 113 patients (48.1%) were male, and the mean (SD) age was 62.65 (11.49) years. In the training set, 186 (39%), 291 (61%), and 359 (75%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 4.21 (95% CI, 3.68-4.90) months. In the validating set, 84 (36%), 120 (51%), and 144 (61%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 5.20 (95% CI, 4.07-7.17) months. Body mass index (18.5 to <25 vs ≥25: hazard ratio [HR], 1.42; 95% CI, 1.14-1.78 and <18.5 vs ≥25: HR, 2.31; 95% CI, 1.56-3.44), histology (non-small cell vs small cell lung cancer: HR, 0.59; 95% CI, 0.41-0.86), epidermal growth factor receptor mutation (positive vs unknown: HR, 0.66; 95% CI, 0.46-0.93 and negative vs unknown: HR, 0.98; 95% CI, 0.66-1.45), smoking status (ever smoker vs never smoker: HR, 1.50; 95% CI, 1.24-1.83), age, and neutrophil to lymphocyte ratio were incorporated. The HRs of age and neutrophil to lymphocyte ratio were modeled nonlinearly with restricted cubic splines (both P < .001). The nomogram's discriminative ability was good in the training set (C statistic, ≥0.77; P < .001) and was validated using both an internal bootstrap method (C statistic, ≥0.76; P < .001) and an external validating set (C statistic, ≥0.75; P < .001). The calibration plots for the end points showed optimal agreement between the nomogram's assessment and actual observations. Conclusions and Relevance: The nomogram (with web-based tool) can be useful for assessing the probability of survival at 3, 6, and 12 months in patients with metastatic lung cancer referred for radiotherapy to treat bone metastases, and it may guide radiation oncologists in treatment decision making and engaging patients in end-of-life discussions and/or hospice referrals at appropriate times.