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.

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.

Initial neutrophil-to-lymphocyte ratio predicts radiation-induced trismus in parotid gland cancer.

OBJECTIVE: To investigate the link between pretreatment neutrophil-to-lymphocyte ratio(NLR) and the incidence of radiation-induced trismus(RIT) in parotid gland cancers(PGC) patients after postoperative radiotherapy(PORT). METHOD: Data of PGC patients who had oral examinations before and after PORT were reviewed retrospectively. We comprised patients who had maximum mouth opening (MMO) assessments before and after PORT and complete blood count test on the first day of PORT. MMO of ≤35 mm was considered as RIT. The receiver operating characteristic (ROC) curve analysis was used to search for an ideal NLR threshold value that might be linked to RIT rates. RESULTS: Fifty-one patients were included, with a RIT incidence of 15.7%. The NLR cutoff that showed a link with the prevalence of RIT in the ROC curve analysis was 2.7[Area under the curve (AUC):82.0%; sensitivity:87.5%; specificity:74.4%]. The patients were divided into groups based on this value:Group 1: NLR≤2.7 (N = 34) and;NLR >2.7 (N = 17). In comparative analysis, the incidence of RIT was found to be statistically higher in the NLR >2.7 than counterpart (35.2%vs.5.8%;rs :0.79; p < .001). Also, a mean temporomandibular joint dose ≥51.0Gy was linked to increased RIT rates (p < .001). CONCLUSION: This study showed that high pre-PORT NLR levels were a robust and independent predictor of significantly elevated rates of RIT.

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.

Hemoglobin-to-platelet ratio in predicting the incidence of trismus after concurrent chemoradiotherapy.

OBJECTIVE: The significance of pre-hemoglobin-to-platelet ratio (HPR) in predicting the occurrence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma patients (LA-NPC) who received concurrent chemoradiotherapy (C-CRT). METHODS: The records of LA-NPC patients with oral examination before and after C-CRT were analyzed. Maximum mouth openings (MMO) were measured before and after C-CRT to confirm RIT status, with an MMO of ≤35 mm defined as RIT. HPR values were calculated on the first day of C-CRT. The relationship between the HPR values and RIT status was discovered using the receiver operating characteristic curve analysis. RESULTS: A total of 43 patients RIT cases among 198 individuals were diagnosed. The optimal HPR cutoff that stratified the patients into two groups was 0.54. RIT incidence was found to be significantly higher in the HPR ≤0.54 group than its HPR >0.54 counterpart(p < 0.001). Univariately T3-4 stage, mean masticator apparatus dose>57.2Gy, and pre-C-CRT MMO ≤40.7 mm were found as the other significant correlates of increased RIT rates(p < 0.05). All four variables seemed to be independently connected to greater RIT incidence in multivariate analysis (p < 0.05, for each). CONCLUSION: The risk of post-C-CRT RIT may be significantly increased when pre-treatment HPR levels are low.

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.

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.

Postchemoradiotherapy Neutrophil-to-Lymphocyte Ratio Predicts Distant Metastasis and Survival Results in Locally Advanced Pancreatic Cancers.

Materials and Methods: Our retrospective research included a sum of 126 LAPAC patients who received CCRT. The NLR was calculated for each patient based on the complete blood count test results obtained on the last day of the CCRT. The availability of optimal cutoff(s) that might dichotomize the whole cohort into two groups with significantly different clinical outcomes was searched using receiver operating characteristic (ROC) curve analysis. Primary and secondary endpoints were the potential association between the post-CCRT NLR measures and distant metastasis-free survival (DMFS) and overall survival (OS) outcomes. Results: The median follow-up duration was 14.7 months (range: 2.4-94.5). The median and 3-year OS and DMFS rates for the whole group were 15.3 months (95% confidence interval: 12.4-18.2) and 14.5%, and 8.7 months (95% CI: 6.7-10.7) and 6.3% separately. The ROC curve analysis findings separated the patients into two groups on a rounded NLR cutoff of 3.1 (area under the curve (AUC): 75.4%; sensitivity: 74.2%; specificity: 73.9%) for OS and DMFS: NLR <3.1 (N = 62) and NLR ≥3.1 (N = 64), respectively. Comparisons between the NLR groups displayed that the median OS (11.4 vs. 21.4 months; P < 0.001) and DMFS (6.0 vs. 16.0 months; P < 0.001) lengths were significantly shorter in the NLR ≥3.1 group than its NLR <3.1 counterparts, as well as the 3-year actuarial DM rate (79.7% vs. 50.0%; P=0.003). The N1-2 nodal stage, CA 19-9>90 U/mL, and NLR >3.1 were found to be independent predictors of poor prognosis in the multivariate analysis. Conclusion: The present study found that the posttreatment NLR ≥3.1 was independently linked with a higher risk of DM and subsequent degraded survival outcomes in unresectable LAPAC patients managed with exclusive CCRT.

Chronically Radiation-Exposed Survivor Glioblastoma Cells Display Poor Response to Chk1 Inhibition under Hypoxia.

Glioblastoma is the most malignant primary brain tumor, and a cornerstone in its treatment is radiotherapy. However, tumor cells surviving after irradiation indicates treatment failure; therefore, better understanding of the mechanisms regulating radiotherapy response is of utmost importance. In this study, we generated clinically relevant irradiation-exposed models by applying fractionated radiotherapy over a long time and selecting irradiation-survivor (IR-Surv) glioblastoma cells. We examined the transcriptomic alterations, cell cycle and growth rate changes and responses to secondary radiotherapy and DNA damage response (DDR) modulators. Accordingly, IR-Surv cells exhibited slower growth and partly retained their ability to resist secondary irradiation. Concomitantly, IR-Surv cells upregulated the expression of DDR-related genes, such as CHK1, ATM, ATR, and MGMT, and had better DNA repair capacity. IR-Surv cells displayed downregulation of hypoxic signature and lower induction of hypoxia target genes, compared to naïve glioblastoma cells. Moreover, Chk1 inhibition alone or in combination with irradiation significantly reduced cell viability in both naïve and IR-Surv cells. However, IR-Surv cells' response to Chk1 inhibition markedly decreased under hypoxic conditions. Taken together, we demonstrate the utility of combining DDR inhibitors and irradiation as a successful approach for both naïve and IR-Surv glioblastoma cells as long as cells are refrained from hypoxic conditions.

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

PURPOSE: The aim of this study was to evaluate the outcomes of 68Ga prostate-specific membrane antigen (68Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC). METHODS: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with 68Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation. RESULTS: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2­year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2­year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT. CONCLUSION: 68Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.

Prognostic Value of Pretreatment Systemic Immune-Inflammation Index in Glioblastoma Multiforme Patients Undergoing Postneurosurgical Radiotherapy Plus Concurrent and Adjuvant Temozolomide.

OBJECTIVES: To evaluate the potential prognostic utility of pretreatment systemic immune-inflammation index (SII) in newly diagnosed glioblastoma multiforme (GBM) patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide. METHODS: The retrospective data of GBM patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide were analyzed. For each patient, SII was calculated using the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SII = platelets × neutrophils/lymphocytes. The receiver operating characteristic (ROC) curve analysis was utilized for the evaluation of optimal cut-off values for SII those linked with the outcomes. Primary and secondary endpoints constituted the overall (OS) and progression-free survival (PFS) per conveyance SII group. RESULTS: A total of 167 patients were included. The ROC curve analysis identified the optimum SII cut-off at a rounded 565 value that significantly interacted with the PFS and OS and stratified patients into two groups: low-SII (SII < 565; n = 71) and high-SII (SII ≥ 565; n = 96), respectively. Comparative survival analyses exhibited that the high-SII cohort had significantly shorter median PFS (6.0 versus 16.6 months; P < 0.001) and OS (11.1 versus 22.9 months; P < 0.001) than the low-SII cohort. The relationship between the high-SII and poorer PFS (P < 0.001) and OS (P < 0.001) further retained its independent significance in multivariate analysis, as well. CONCLUSIONS: The outcomes displayed here qualified the pretreatment SII as a novel independent prognostic index for predicting survival outcomes of newly diagnosed GBM patients undergoing postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide.

Ovarian and Uterine Functions in Female Survivors of Childhood Cancers.

Adult survivors of childhood cancers are more prone to developing poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. Chemotherapy drugs exert cytotoxic effects systemically and therefore can damage the ovaries, leading to infertility, premature ovarian failure, and, to a lesser extent, spontaneous abortions. They have very limited or no deleterious effects on the uterus that can be recognized clinically. By contrast, radiation is detrimental to both the ovaries and the uterus, thereby causing a greater magnitude of adverse effects on the female reproductive function. These include infertility, premature ovarian failure, miscarriage, fetal growth restrictions, perinatal deaths, preterm births, delivery of small-for-gestational-age infants, preeclampsia, and abnormal placentation. Regrettably, the majority of these adverse outcomes arise from radiation-induced uterine injury and are reported at higher incidence in the adult survivors of childhood cancers who were exposed to uterine radiation during childhood in the form of pelvic, spinal, or total-body irradiation. Recent findings of long-term follow-up studies evaluating reproductive performance of female survivors provided some reassurance to female cancer survivors by documenting that pregnancy and live birth rates were not significantly compromised in survivors, including those who had been treated with alkylating agents and had not received pelvic, cranial, and total-body irradiation. We aimed in this narrative review article to provide an update on the impact of chemotherapy and radiation on the ovarian and uterine function in female survivors of childhood cancer. IMPLICATIONS FOR PRACTICE: Adult survivors of childhood cancers are more prone to developing a number of poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. The impact of radiation therapy on the female genital system is greater than chemotherapy regimens because radiation is detrimental to both the uterus and the ovaries, whereas toxic effects of chemotherapy drugs are confined to the ovaries. Therefore, radiation-induced uterine damage accounts for most poor obstetrical outcomes in the survivors. These include infertility, miscarriages, stillbirths, fetal growth restrictions, preeclampsia, and preterm deliveries.

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

INTRODUCTION: To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). METHODS: Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. RESULTS: A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001). CONCLUSIONS: The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.