Pre-chemoradiotherapy high platelet counts predict jaw osteoradionecrosis in locally advanced nasopharyngeal carcinoma patients.

INTRODUCTION: This retrospective study aimed to investigate if pretreatment platelet (PLT) levels can predict the risk of osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) who received concurrent chemoradiotherapy (CCRT). MATERIAL &METHODS: ORNJ instances were identified from LA-NPC patients' pre- and post-CCRT oral exam records. All pretreatment PLT values were acquired on the first day of CCRT. Receiver operating characteristic curve analysis was used to determine the optimal PLT cutoff that divides patients into two subgroups with distinctive ORNJ rates. The primary outcome measure was the association between pretreatment PLT values and ORNJ incidence rates. RESULTS: The incidence of ORNJ was 8.8 % among the 240 LA-NPC patients analyzed. The ideal pre-CCRT PLT cutoff which divided the patients into two significantly different ORNJ rate groups was 285,000 cells/µL (PLT ≤ 285,000 cells/µL (N = 175) vs. PLT > 285,000 cells/µL (N = 65)). A comparison of the two PLT groups revealed that the incidence of ORNJ was substantially higher in patients with PLT > 285,000 cells/L than in those with PLT≤285,000 cells/L (26.2% vs. 2.3 %; P < 0.001). The presence of pre-CCRT ≥3 tooth extractions, any post-CCRT tooth extractions, mean mandibular dose ≥ 34.1 Gy, mandibular V57.5 Gy ≥ 34.7 %, and post-CCRT tooth extractions > 9 months after CCRT completion were also associated with significantly increased ORNJ rates. A multivariate Cox regression analysis demonstrated that each characteristic had an independent significance on ORNJ rates after CCRT. CONCLUSION: An affordable and easily accessible novel biomarker, PLT> 285,000 cells/L, may predict substantially higher ORNJ rates after definitive CCRT in individuals with LA-NPC.

The Use of Pre-Chemoradiotherapy Total Masseter Muscle Volume as a Novel Predictor of Radiation-Induced Trismus in Locally Advanced Nasopharyngeal Carcinoma Patients.

BACKGROUND: We sought to determine whether pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). METHODS: We retrospectively reviewed the medical records of LA-NPC patients who received C-CRT and had pretreatment maximum mouth openings (MMO) greater than 35 mm. MMO of 35 mm or less after C-CRT were considered RIT. We employed receiver operating characteristic (ROC) curve analysis to explore the correlation between pre-treatment TMMV readings and RIT status. RESULTS: Out of the 112 eligible patients, 22.0% of them received a diagnosis of RIT after C-CRT. The optimal TMMV cutoff that was significantly linked to post-C-CRT RIT rates was determined to be 35.0 cc [area under the curve: 79.5%; sensitivity: 75.0%; and specificity: 78.6%; Youden index: 0.536] in the ROC curve analysis. The incidence of RIT was significantly higher in patients with TMMV ≤ 5.0 cc than in those with TMMV > 35.0 cc [51.2% vs. 8.7%; Odds ratio: 6.79; p < 0.001]. A multivariate logistic regression analysis revealed that pre-C-CRT MMO ≤ 41.6 mm (p = 0.001), mean masticatory apparatus dose V56.5 ≥ 34% group (p = 0.002), and TMMV ≤ 35 cc were the independent predictors of significantly elevated rates of RIT. CONCLUSION: The presence of a smaller pretreatment TMMV is a reliable and independent novel biological marker that can confidently predict higher RIT rates in LA-NPC patients who receive C-CRT.

Predictive potential of pan-immune-inflammation value / hemoglobin index as biomarker for osteoradionecrosis risk in locally advanced nasopharyngeal carcinomas.

OBJECTIVE: We aimed to investigate whether the Pan-Immune-Inflammation-Value/Hemoglobin (PIV/Hb) index could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal cancer (LA-NPC). MATERIALS AND METHODS: This retrospective analysis included LA-NPC patients who underwent CCRT and pre-CCRT oral exams at our institution's Departments of Radiation Oncology and Dentistry between January 2010 and December 2022. The relationship between ORN rates and PIV-Hb levels was explored using receiver operating characteristic curve analysis. The primary objective was to establish a correlation between pre-CCRT PIV-Hb levels and ORN rates, while the secondary objective was to identify other risk factors for ORN. RESULTS: Of 249 eligible patients, 21 (8.4 %) were diagnosed with ORN. The optimal pre-CCRT PIV/Hb cutoff was 73.8, which divided patients into two subgroups with distinctive ORN risk estimates: Group 1: PIV/Hb < 73.8 (N = 206), and Group 2: PIV/Hb ≥ 73.8 (N = 43). The results of the comparative analysis indicated that the cohort with PIV/Hb ≥ 73.8 exhibited substantially higher rates of ORN than the PIV/Hb < 73.8 cohort (44.2 % vs. 1.0 %; P < 0.001). The multivariate logistic regression analysis indicated that the pretreatment PIV/Hb ≥ 73.8 was independently associated with higher ORN rates (P < 0.001). CONCLUSION: The results of our current investigation indicate that higher levels of pretreatment PIV/Hb were associated with a significant independent increase in ORN rates in LA-NPC patients who received CCRT.

High pre-chemoradiotherapy pan-immune-inflammation value levels predict worse outcomes in patients with stage IIIB/C non-small-cell lung cancer.

BACKGROUND AND OBJECTIVES: We explored the prognostic usefulness of the pan-immune-inflammation value (PIV) in patients with stage IIIB/C non-small-cell lung cancer (NSCLC) who underwent concurrent chemoradiotherapy (CCRT). METHODS AND PATIENTS: For all patients, the PIV was calculated using platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) measures obtained on the first day of CCRT: PIV = P × M × N ÷ L. Using receiver operating characteristic (ROC) curve analysis, we searched for the existence of an ideal cutoff that may partition patients into two groups with unique progression-free- (PFS) and overall survival (OS) results. The primary endpoint of this retrospective cohort research was to determine whether there were any significant relationships between pretreatment PIV measures and post-CCRT OS outcomes. RESULTS: The present research included a total of 807 stage IIIB/C NSCLC patients. According to ROC curve analysis, the ideal PIV cutoff was 516 [area under the curve (AUC): 67.7%; sensitivity: 66.4%; specificity: 66.1%], which divided the whole cohort into two: low PIV (L-PIV: PIV < 516; N = 436) and high PIV (H-PIV: PIV ≥ 516; N = 371). The comparisons between the PIV groups indicated that either the median PFS (9.2 vs. 13.4 months; P < 0.001) or OS (16.7 vs. 32.7 months; P < 0.001) durations in the H-PIV group were substantially inferior to their L-PIV counterpart. Apart from the H-PIV (P < 0.001), the N3 nodal stage (P = 0.006), IIIC disease stage (P < 0.001), and receiving only one cycle of concurrent chemotherapy (P = 0.005) were also determined to be significant predictors of poor PFS (P < 0.05, for each) and OS (P < 0.05, for each) outcomes in univariate analysis. The multivariate analysis findings revealed that all four variables had independent negative impacts on PFS (P < 0.05, for each) and OS (P < 0.05, for each). CONCLUSIONS: The findings of this hypothesis-generating retrospective analysis claimed that the novel PIV was an independent and steadfast predictor of PFS and OS in stage IIIB/C NSCLC patients.

The Prognostic Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) in Stage IIIC Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy.

BACKGROUND: We sought to determine the prognostic value of the newly developed Global Immune-Nutrition-Inflammation Index (GINI) in patients with stage IIIC non-small cell lung cancer (NSCLC) who underwent definitive concurrent chemoradiotherapy (CCRT). METHODS: This study was conducted on a cohort of 802 newly diagnosed stage IIIC NSCLC patients who underwent CCRT. The novel GINI created first here was defined as follows: GINI = [C-reactive protein × Platelets × Monocytes × Neutrophils] ÷ [Albumin × Lymphocytes]. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal pre-CCRT GINI cut-off value that substantially interacts with the locoregional progression-free (LRPFS), progression-free (PFS), and overall survival (OS). RESULTS: The optimal pre-CCRT GINI cutoff was 1562 (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%; Youden index: 0.406). Patients presenting with a GINI ≥ 1562 had substantially shorter median LRPFS (13.3 vs. 18.4 months; p < 0.001), PFS (10.2 vs. 14.3 months; p < 0.001), and OS (19.1 vs. 37.8 months; p < 0.001) durations than those with a GINI < 1562. Results of the multivariate analysis revealed that the pre-CCRT GINI ≥ 1562 (vs. <1562), T4 tumor (vs. T3), and receiving only 1 cycle of concurrent chemotherapy (vs. 2-3 cycles) were the factors independently associated with poorer LRPS (p < 0.05 for each), PFS (p < 0.05 for each), and OS (p < 0.05 for each). CONCLUSION: The newly developed GINI index efficiently divided the stage IIIC NSCLSC patients into two subgroups with substantially different median and long-term survival outcomes.

Utility of pre-chemoradiotherapy Pan-Immune-Inflammation-Value for predicting the osteoradionecrosis rates in locally advanced nasopharyngeal cancers.

PURPOSE: The aim of this retrospective study was to explore whether pretreatment Pan-Immune-Inflammation-Value (PIV) measurements might predict the risk of mandibular osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal cancer (LA-NPC). METHODS: The platelet, monocyte, neutrophil, and lymphocyte counts acquired on the first day of CCRT were used to compute pretreatment PIV levels: PIV = (Plateletsâ€¯× Monocytesâ€¯× Neutrophils) ÷ Lymphocytes. Receiver operating characteristic curve analysis was used to determine the association between ORN rates and PIV levels. Spearman correlation analysis was used to examine the probable intergroup correlations. The potential link between the pretreatment PIV levels and the post-treatment ORN rates was determined as the primary objective. RESULTS: 21 (10.0%) of 210 eligible patients were diagnosed with ORN. The optimal pre-CCRT PIV cutoff was 833, which separated patients into two PIV groups with divergent ORN prevalence estimates: Group 1: PIV < 833 (N = 153), and Group 2: PIV ≥ 833 (N = 57). The comparison analysis found that the PIV ≥ 833 cohort had significantly higher ORN rates than the PIV < 833 cohort (29.8% vs. 2.6%; P < 0.001). Other characteristics linked to significantly higher ORN rates were the patient's continuing smoking, the use of the Three-dimensional conformal radiation therapy technique, the mean mandibular dose of ≥ 58.1 Gy, the number of tooth extractions before CCRT ≥ 4, and the presence of tooth extractions after CCRT. The independent importance of all factors on higher ORN occurrence rates were retained in multivariate analysis (P < 0.05). CONCLUSIONS: Our findings revealed a strong link between aggravated inflammatory response and ORN genesis, with high pretreatment PIV levels related to significantly higher ORN rates.

A high pan-immune-inflammation value before chemoradiotherapy indicates poor outcomes in patients with small-cell lung cancer.

Objectives: The objective of our study was to assess the prognostic significance of the Pan-Immune-Inflammation Value (PIV) before concurrent chemoradiation (C-CRT) and prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC). Methods: The medical records of LS-SCLC patients who underwent C-CRT and PCI between January 2010 and December 2021 were retrospectively analyzed. PIV values were calculated using the peripheral blood samples obtained within the past 7 days before the initiation of treatment: PIV = [neutrophils × platelets × monocytes] ÷ lymphocytes. Using receiver operating characteristic (ROC) curve analysis, the optimal pretreatment PIV cutoff values that can partition the study population into two groups with substantially distinct progression-free survival (PFS) and overall survival (OS) outcomes were determined. The relationship between PIV values and OS outcomes was the primary outcome measure. Results: Eighty-nine eligible patients were divided into two PIV groups at an optimal cutoff of 417 [Area under curve (AUC): 73.2%; sensitivity: 70.4%; specificity: 66.7%]: Group 1: PIV < 417 (N = 36) and Group 2: PIV ≥ 417 (N = 53). Comparative analyses revealed that patients with PIV < 417 had significantly longer OS (25.0 vs 14.0 months, p < .001) and PFS (18.0 vs 8.9 months, p = .004) compared to patients with PIV ≥ 417. The outcomes of the multivariate analysis have verified the independent significance of pretreatment PIV concerning PFS (p < .001) and OS (p < .001) outcomes. Conclusion: The findings of this retrospective study indicate that the pretreatment PIV is a reliable and independent prognostic biomarker for patients with LS-SCLC who were treated with C-CRT and PCI.

Valero's host index is useful in predicting radiation-induced trismus and osteoradionecrosis of the jaw risks in locally advanced nasopharyngeal carcinoma patients.

BACKGROUND: In the absence of previous research, we sought to assess the H-Index's predictive significance for radiation-induced trismus (RIT) and osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). PATIENTS AND METHODS: The research comprised 295 LA-NPC patients who had C-CRT and pre- and post-C-CRT oral exams between June 2010 and December 2021. The H-Index was calculated using neutrophils, monocytes, lymphocytes, hemoglobin, and albumin measurements obtained on the first day of C-CRT. Patients were divided into three and two H-index groups, respectively, based on previously established cutoff values (1.5 and 3.5) and the cutoff value determined by our receiver operating characteristic (ROC) curve analysis. The primary objective was the presence of any significant connections between pretreatment H-Index groups and post-C-CRT RIT and ORNJ rates. RESULTS: RIT and ORNJ was diagnosed in 46 (15.6%) and 13 (7.8%) patients, respectively. The original H-Index grouping could only categorize RIT and ORNJ risks at a cutoff value of 3.5, with no significant differences in RIT and ORNJ rates between groups with H-Index 1.5 and 1.5 to 3.5 (P < 0.05 for each). The ideal H-Index cutoff for both RIT and ORNJ rates was found to be 5.5 in ROC curve analysis, which divided the entire research population into two groups: H-Index ≤ 5.5 (N = 195) and H-Index > 5.5 (N = 110). Intergroup comparisons revealed that patients in the H-Index > 5.5 group had significantly higher rates of either RIT (31.8% vs. 5.9%; P < 0.001) or ORNJ (17.3% vs. 2.2%; P < 0.001) than their H-Index ≤ 5.5 counterparts. The results of the multivariate analysis showed that H-Index > 5.5 was independently linked to significantly higher RIT (P < 0.001) and ORNJ (P < 0.001) rates. CONCLUSION: Pre-C-CRT H-Index > 5.5 is associated with significantly increased RIT and ORNJ rates in LA-NPC patients receiving definitive C-CRT.

Low hemoglobin levels predict increased radiation-induced trismus rates in nasopharyngeal cancer.

PURPOSE: To investigate the predictive significance of hemoglobin (Hb) values in the incidence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients who received concurrent chemoradiotherapy (C-CRT). METHODS: Data of LA-NPC patients were examined before and after C-CRT and to confirm the presence of RIT, maximum mouth openings (MMO) were measured; RIT is defined as an MMO of ≤35 mm. All Hb values were derived from complete blood count tests obtained on the first day of C-CRT. The receiver operating characteristic (ROC) curve analysis was used to scrutinize a possible connection between pre-treatment Hb values and RIT status. RESULTS: Two hundred and twenty three patients were included in the study and RIT was diagnosed in 46 (20.6%) patients. The Hb cutoff in ROC curve analysis that separated the patients into two groups was 12.05 g/dL [Area under the curve (AUC): 82.7%; sensitivity: 72.9%; and specificity: 71.3%]. RIT was significantly more prevalent in the Hb ≤ 12 g/dL group than in its counterpart (41.9% vs. 7.3%; p < 0.001). In multivariate analysis, Hb ≤ 12, anemia, pre-C-CRT MMO < 41.4 mm, and masticatory apparatus doseV58 Gy < 32% groups were found to be independently associated with significantly increased rates of RIT. CONCLUSION: Low pre-C-CRT Hb and anemia status are novel biological markers that independently predict higher RIT rates in LA-NPC undergoing C-CRT.

The predictive usefulness of the novel "combined hemoglobin-to-platelet ratio and maximum mouth opening index" on prevalence of radiation induced trismus in patients with nasopharyngeal cancer.

OBJECTIVES: To explore how well a unique combination of hemoglobin-to-platelet ratio (HPR) and pretreatment maximum mouth opening (MMO) predicts the prevalence of radiation-induced trismus (RIT). PATIENTS AND METHODS: HPR and MMO cutoff values (0.54 and 40.7 mm) divided patients into two groups. To develop the novel HPR-MMO index, four combinations of these factors were tested for predictive power: Group 1: HPR > 0.54 and MMO > 40.7 mm; Group 2: HPR ≤ 0.54 but MMO > 40.7 mm; Group 3: HPR > 0.54 but MMO ≤ 40.7 mm; Group 4: HPR ≤ 0.54 and MMO ≤ 40.7 mm. RESULTS: Data of 198 patients with LA-NPC was analyzed retrospectively. RIT rates for Groups 1 to 4 were 10.2%, 15.2%, 25%, and 59.4%. Groups 2 and 3 were merged to generate HPR-MMO index because of statistically equivalent RIT rates: Low-risk: HPR > 0.54 and MMO > 40.7 mm; Intermediate-risk: HPR ≤ 0.54 but MMO > 40.7 mm or; HPR > 0.54 but MMO ≤ 40.7 mm; High-risk: HPR ≤ 0.54 and MMO ≤ 40.7 mm. It was revealed that the low-, high-, and intermediate-risk group's RIT rates; 10.2%, 59.4%, and 19.2%, respectively. CONCLUSION: The novel HPR-MMO index may to classify LA-NPC patients into low, intermediate, and high-risk RIT groups.

Review of Osteoradionecrosis of the Jaw: Radiotherapy Modality, Technique, and Dose as Risk Factors.

Radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) is the cornerstone of organ-sparing or adjuvant therapy for nearly all head and neck cancers. Unfortunately, aggressive RT or CCRT can result in severe late toxicities, such as osteoradionecrosis of the jaws (ORNJ). The incidence of ORNJ is currently less than 5-6% due to advances in dental preventive care programs, RT planning systems, and RT techniques. Although numerous patient-, tumor-, and treatment-related factors may influence the incidence rates of ORNJ, RT modality (equipment), technique, and dose-volume-related factors are three of the most influential factors. This is mainly because different RT equipment and techniques have different levels of success at delivering the prescribed dose to the focal volume of the treatment while keeping the "organ at risk" safe. ORNJ risk is ultimately determined by mandibular dose, despite the RT technique and method being known predictors. Regardless of the photon delivery method, the radiobiological effects will be identical if the total dose, dose per fraction, and dose distribution within the tissue remain constant. Therefore, contemporary RT procedures mitigate this risk by reducing mandibular dosages rather than altering the ionizing radiation behavior in irradiated tissues. In light of the paucity of studies that have examined the impact of RT modality, technique, and dose-volume-related parameters, as well as their radiobiological bases, the present review aims to provide a comprehensive overview of the published literature on these specific issues to establish a common language among related disciplines and provide a more reliable comparison of research results.

The predictive value of pretreatment hemoglobin-to-platelet ratio on osteoradionecrosis incidence rates of locally advanced nasopharyngeal cancer patients managed with concurrent chemoradiotherapy.

BACKGROUND: This retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: ORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors. RESULTS: We distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months. CONCLUSION: Low pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.

Pre-chemoradiotherapy low hemoglobin levels indicate increased osteoradionecrosis risk in locally advanced nasopharyngeal cancer patients.

PURPOSE: We aimed to determine whether pretreatment hemoglobin (Hb) levels can predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: ORN cases were identified from the records of LA-NPCs who had oral exams before and after CCRT. All Hb measurements were obtained on the first day of treatment. Receiving operating characteristic curve analysis was used to determine the relationship between Hb levels and ORN rates. The relationship between pretreatment Hb levels and ORN rates served as the primary endpoint, and secondary endpoints included the discovery of additional potential ORN risk factors. RESULTS: Among the 263 eligible LA-NPCs, we identified 8.7% ORN cases. The ideal cutoff Hb before CCRT was 10.6 g/dL. It was revealed that HPR ≤ 10.6 group had a significantly higher ORN rate (32.5% vs. 1.5% for Hb > 10.6; P < 0.001). The mandibular V59.8 ≥ 36% Gy, pre-CCRT ≥ 4 tooth extractions, the presence of post-CCRT tooth extractions, and the time of post-CCRT tooth extractions > 8 months were the other factors associated with significantly increased ORN rates (P < 0.05 for each). CONCLUSION: Low pre-CCRT Hb levels appeared to be independently linked to significantly higher ORN rates. Pretreatment Hb levels may be used to establish preventive measures and predict ORN.