A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

PURPOSE: To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5 years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. METHODS: This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. RESULTS: The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12 g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12 g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. CONCLUSIONS: The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

Impact of Varying Chest Wall Target Volume Delineation on Postmastectomy Radiation Therapy Outcomes in Breast Cancer Patients with Implant-Based Reconstruction.

BACKGROUND: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. Traditionally, the RT chest wall (CW) volume encompasses the entire implant. For patients with retropectoral implants, the deep lymphatic plexus dorsal part of the implant is no longer considered high risk and can be omitted. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different CW delineation according to ESTRO ACROP guideline for patients who have undergone implant-based reconstruction. METHODS: We conducted a retrospective review of breast cancer patients who underwent a mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. RESULTS: The study included 26 patients, with 15 in the prepectoral group and 11 in the whole expander group. No significant differences were observed in normal organ exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p = 0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. CONCLUSIONS: For patients undergoing two-stage expander/implant retropectoral breast reconstruction and PMRT, our data provided comparable outcomes and normal organ exposure for those omitting the deep lymphatic plexus.

Ultrasound Is Beneficial to Determine Lymphadenopathy in Oral Cancer Patients after Radiotherapy.

The present study aimed to investigate whether the addition of ultrasound (US) +/- fine needle aspiration (FNA) to magnetic resonance imaging (MRI) or computed tomography (CT) improves the diagnostic accuracy in assessing neck lymphadenopathy in oral cancer patients after neck irradiation. We retrospectively reviewed oral cancer patients who had neck lymphadenopathy after radiotherapy (RT) or chemoradiation therapy (CRT) from February 2008 to November 2019. The following diagnostic modalities were assessed: (1) MRI/CT, (2) MRI/CT with a post-RT US predictive model, and (3) MRI/CT with US + FNA. The receiver operating characteristic (ROC) curves were used to assess the diagnostic performance. A total of 104 irradiation-treated oral cancer patients who subsequently had neck lymphadenopathy were recruited and analyzed. Finally, there were 68 (65%) malignant and 36 (35%) benign lymphadenopathies. In terms of the diagnostic performance, the area under the ROC curves (C-statistics) was 0.983, 0.920, and 0.828 for MRI/CT with US + FNA, MRI/CT with a post-RT US predictive model, and MRI/CT, respectively. The addition of US to MRI/CT to evaluate cervical lymphadenopathy could achieve a better diagnostic accuracy than MRI/CT alone in oral cancer patients after neck irradiation.

Postchemoradiotherapy systemic inflammation response index predicts treatment response and overall survival for patients with locally advanced nasopharyngeal cancer.

BACKGROUND/PURPOSE: To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal cancer (NPC). METHODS: A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival. RESULTS: Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p = 0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p = 0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p = 0.017). CONCLUSION: The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.

Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer.

In this study, we determined the diagnostic performance of adding ultrasound (US) with/without fine-needle aspiration cytology (FNAC) to computed tomography (CT)/magnetic resonance imaging (MRI) in evaluating neck lymphadenopathy (LAP) in patients with head and neck cancer treated with irradiation. We included 269 patients who had neck LAP after radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) resulting from cancers of the head and neck region between October 2008 and September 2018. The diagnostic methods consisted of the following: 1) CT/MRI alone, 2) CT/MRI combined with a post-RT US predictive model, and 3) CT/MRI combined with US + FNAC. We compared their diagnostic performance using receiver operating characteristic (ROC) curves. In total, 141 (52%) malignant and 128 (48%) benign LAPs were observed. Regarding the diagnostic accuracy, the area under the ROC curves was highest for the combined CT/MRI and US + FNAC (0.965), followed by the combined CT/MRI and post-RT US predictive model (0.906) and CT/MRI alone (0.836). Our data suggest that the addition of a US examination to CT/MRI resulted in higher diagnostic performance than CT/MRI alone in terms of diagnosing recurrent or persistent nodal disease during the evaluation of LAP in patients with irradiation-treated head and neck cancer.

IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.

Total Skin Treatment with Helical Arc Radiotherapy.

For widespread cutaneous lymphoma, such as mycosis fungoides or leukemia cutis, in patients with acute myeloid leukemia (AML) and for chronic myeloproliferative diseases, total skin irradiation is an efficient treatment modality for disease control. Total skin irradiation aims to homogeneously irradiate the skin of the entire body. However, the natural geometric shape and skin folding of the human body pose challenges to treatment. This article introduces treatment techniques and the evolution of total skin irradiation. Articles on total skin irradiation by helical tomotherapy and the advantages of total skin irradiation by helical tomotherapy are reviewed. Differences among each treatment technique and treatment advantages are compared. Adverse treatment effects and clinical care during irradiation and possible dose regimens are mentioned for future prospects of total skin irradiation.

Local Liver Irradiation Concurrently Versus Sequentially with Cabozantinib on the Pharmacokinetics and Biodistribution in Rats.

The aim of this study was to evaluate the radiotherapy (RT)-pharmacokinetics (PK) effect of cabozantinib in concurrent or sequential regimens with external beam radiotherapy (EBRT) or stereotactic body radiation therapy (SBRT). Concurrent and sequential regimens involving RT and cabozantinib were designed. The RT-drug interactions of cabozantinib under RT were confirmed in a free-moving rat model. The drugs were separated on an Agilent ZORBAX SB-phenyl column with a mobile phase consisting of 10 mM potassium dihydrogen phosphate (KH2PO4)-methanol solution (27:73, v/v) for cabozantinib. There were no statistically significant differences in the concentration versus time curve of cabozantinib (AUCcabozantinib) between the control group and the RT2Gy×3 f'x and RT9Gy×3 f'x groups in the concurrent and the sequential regimens. However, compared to those in the control group, the Tmax, T1/2 and MRT decreased by 72.8% (p = 0.04), 49.0% (p = 0.04) and 48.5% (p = 0.04) with RT2Gy×3 f'x in the concurrent regimen, respectively. Additionally, the T1/2 and MRT decreased by 58.8% (p = 0.01) and 57.8% (p = 0.01) in the concurrent RT9Gy×3 f'x group when compared with the control group, respectively. The biodistribution of cabozantinib in the heart increased by 271.4% (p = 0.04) and 120.0% (p = 0.04) with RT2Gy×3 f'x in the concurrent and sequential regimens compared to the concurrent regimen, respectively. Additionally, the biodistribution of cabozantinib in the heart increased by 107.1% (p = 0.01) with the RT9Gy×3 f'x sequential regimen. Compared to the RT9Gy×3 f'x concurrent regimen, the RT9Gy×3 f'x sequential regimen increased the biodistribution of cabozantinib in the heart (81.3%, p = 0.02), liver (110.5%, p = 0.02), lung (125%, p = 0.004) and kidneys (87.5%, p = 0.048). No cabozantinib was detected in the brain in any of the groups. The AUC of cabozantinib is not modulated by irradiation and is not affected by treatment strategies. However, the biodistribution of cabozantinib in the heart is modulated by off-target irradiation and SBRT doses simultaneously. The impact of the biodistribution of cabozantinib with RT9Gy×3 f'x is more significant with the sequential regimen than with the concurrent regimen.

Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin's Lymphoma.

BACKGROUND: A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin's lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin's lymphoma by analyzing the metabolic activity of adipose tissue. METHODS: Twenty patients who received R-CHOP for non-Hodgkin's lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. RESULTS: The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). CONCLUSIONS: The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.

Speech and Swallowing Rehabilitation Potentially Decreases Body Weight Loss and Improves Survival in Head and Neck Cancer Survivors.

This retrospective observational cohort study aims to assess the outcomes and associated factors in head and neck cancer (HNC) survivors with dysphagia, and to investigate the relationship between outcomes and speech and swallowing rehabilitation (SSR). We enrolled patients who were diagnosed with HNC between October 2016 and July 2018; we included 393 patients who developed dysphagia after definite treatment and were referred to speech-language pathologists (SLPs). We then classified patients into groups according to whether they received SSR. We used the clinical variables-including age, sex, site of malignancy, cancer stage, treatment modality, SSR, initial ECOG score, initial KPS, initial body weight (BW), and initial BMI-to evaluate the association between the percentage of BW change and overall survival (OS). There were 152 (39%) and 241 (61%) patients who received and did not receive SSR, respectively. In multivariate linear regression, SSR was significantly associated with percentage change in BW at 3 months post-treatment. Having SSR was positively associated with the percentage change in BW and decreased the BW loss [ß coefficient (95% CIs) = 2.53 (0.92 to 4.14)] compared to having no SSR. In the multivariate Cox regression, SSR was an independent factor for OS. Compared to no SSR, the hazard ratio (95% CIs) for patients who received SSR was 0.48 (0.31 to 0.74). SSR helps to avoid BW loss and increases overall survival. HNC patients who develop dysphagia after treatment should be encouraged to participate in SSR.

Fatal rectovaginal fistula in post-radiotherapy locally advanced cervical cancer patients.

OBJECTIVE: To present the detailed history of three cervical cancer patients with rectovaginal fistula, who had undergone radiotherapy. CASES REPORT: A 74-year-old patient with end-stage renal disease undergoing hemodialysis had radiotherapy for her advanced cervical cancer. Colonoscopic biopsy showed radiation sigmoid colitis and ulcers. Laparotomy revealed colon perforation and rectovaginal fistula. The second case is a 54-year-old cervical cancer patient, who had received concurrent chemoradiation therapy and further systemic therapy with cisplatin, paclitaxel, and bevacizumab. She suffered from bloody stool and abdominal pain. Rectovaginal fistula was found during exploratory laparotomy. The third case is a 35-year-old cervical cancer patient, who had received concurrent chemoradiation therapy. Systemic therapy was then prescribed with platinum, paclitaxel, and bevacizumab for her lung metastasis, and a rectovaginal fistula was found later. All three patients did not survive later. CONCLUSIONS: Fatal rectovaginal fistula may occur in post-radiation advanced cervical cancer patients. Unnecessary colonoscopic biopsy may cause significant sequelae. In patients with high risk for rectovaginal fistulas, chemotherapy without adding bevacizumab might be suggested in patients with low risk of poor response to chemotherapy. In addition, three-dimensional conformal radiation therapy or intensity-modulated radiation therapy should be used for patients with high risk for fistulas.

Case report: Stereotactic body radiation therapy with 12 Gy for silencing refractory ventricular tachycardia.

Background: Encouraging results have been reported for the treatment of ventricular tachycardia (VT) with stereotactic body radiation therapy (SBRT) with 25 Gy. SBRT with 12 Gy for refractory VT was designed to reduce long-term cardiac toxicity. Methods: Stereotactic body radiation therapy-VT simulation, planning, and treatment were performed using standard techniques. A patient was treated with a marginal dose of 12 Gy in a single fraction to the planning target volume (PTV). The goal was for at least ≥ 95% of the PTV to be covered by at least 95% of 12 Gy radiation. Results: From April 2021 through June 2022, a patient with refractory VT underwent treatment. The volume for PTV was 65.8 cm3. The mean radiation dose administered to the heart (the heart volume excluding the PTV) was 2.2 Gy. No acute or late toxicity was observed after SBRT. Six months after SBRT, the patient experienced new monomorphic right ventricular outflow tract (RVOT) VT. Interestingly, the substrate of the left ventricular basal to middle posteroseptal wall before SBRT was turned into scar zones with a local voltage < 0.5 mV. Catheter ablation to treat RVOT VT was performed, and the situation remains stable to date. Conclusion: This study reports the first patient with refractory VT successfully treated with 12.0 Gy SBRT, suggesting that 12 Gy is a potential dose to treat refractory VT. Further investigations and enrollment of more patients are warranted to assess the long-term efficacy and side effects of this treatment.

Spotted Temporal Lobe Necrosis following Concurrent Chemoradiation Therapy Using Image-Guided Radiotherapy for Nasopharyngeal Carcinoma.

Background: To explore spotted temporal lobe necrosis (TLN) and changes in brain magnetic resonance imaging (MRI) after image-guided radiotherapy (IGRT) in a patient with nasopharyngeal carcinoma (NPC). Case presentation: a 57-year-old male was diagnosed with stage III NPC, cT1N2M0, in 2017. He underwent concurrent chemoradiation therapy (CCRT) with cisplatin (30 mg/m2) and 5- fluorouracil (5-FU, 500 mg/m2) plus IGRT with 70 Gy in 35 fractions for 7 weeks. The following MRI showed a complete response in the NPC. However, the patient suffered from fainting periodically when standing up approximately 3 years after CCRT. Neck sonography showed mild atherosclerosis (< 15%) of bilateral carotid bifurcations and bilateral small-diameter vertebral arteries, with reduced flow volume. The following MRI showed a 9 mm × 7 mm enhancing lesion in the right temporal lobe without locoregional recurrence, and TLN was diagnosed. The lesion was near the watershed area between the anterior temporal and temporo-occipital arteries. The volume of the necrotic lesion was 0.51 c.c., and the mean dose and Dmax of the lesion were 64.4 Gy and 73.7 Gy, respectively. Additionally, the mean dose, V45, D1 c.c. (dose to 1 ml of the temporal lobe volume), D0.5 c.c. and Dmax of the right and left temporal lobes were 11.1 Gy and 11.4 Gy, 8.5 c.c. and 6.7 c.c., 70.1 Gy and 67.1 Gy, 72.0 Gy and 68.8 Gy, and 74.2 Gy and 72.1 Gy, respectively. Conclusion: Spotted TLN in patients with NPC treated by IGRT may be difficult to diagnose due to a lack of clinical symptoms and radiological signs. Endothelial damage may occur in carotid and vertebral arteries within the irradiated area, affecting the small branches supplying the temporal lobe and inducing spotted TLN. Future research on the relationship between vessels and RT or CCRT and the development of TLN is warranted.

Advances in Image-Guided Radiotherapy in the Treatment of Oral Cavity Cancer.

Image-guided radiotherapy (IGRT) is an advanced auxiliary radiotherapy technique. During cancer treatment, patients with oral cavity cancer (OCC) experience not only disease but also adverse effects due to RT. IGRT provides the relevant advantages of RT by precisely delivering tumoricidal doses via real-time knowledge of the target volume location and achieves maximal tumor control with minimal complications as recommended for cancer treatment. Additionally, studies have shown that IGRT can improve clinical outcomes in terms of not only treatment side effects but also survival benefits for cancer patients. IGRT can be performed alongside various imaging methods, including computed tomography and magnetic resonance imaging, and at different times during the radiotherapy regimen. This article reviews the literature to discuss the effects and importance of IGRT for patients with OCC, examines the rationale underlying the advantages of IGRT, discusses the limitations of IGRT with respect to different techniques, and summarizes the strategies and future prospects of IGRT in the treatment of OCC.

Risk of CVD Following Radiotherapy for Head and Neck Cancer: An Updated Systematic Review and Meta-Analysis.

Background: The relative risk for cerebrovascular disease (CVD) is increased in patients with head and neck cancer (HNC) treated with radiotherapy (RT). However, the current relative risk for CVD following RT has not been well clarified. The purpose of this study was to analyze the effect of RT and update the risk of CVD following RT in HNC patients through a systematic review and meta-analysis. Material and Methods: We conducted an online database search and systematic review of observational studies that reported on CVD and extracranial carotid stenosis in patients with HNC who had undergone RT. Articles published in Medline and PubMed from 1980 to 2021 were identified and collected. Results: Of the forty-seven articles identified from PubMed and forty-four articles identified from 3 systematic reviews, twenty-two studies were included. We found that neck RT was a significant risk factor for CVD (HR 3.97, 95% CI: 2.89-5.45). Patients with HNC treated by RT had an increased OR (7.36, 95% CI: 4.13-13.11) for CVD, and approximately 26% (95% CI: 22%-31%) of HNC patients treated with RT were at risk for CVD with more than 50% reduction in carotid diameter. Conclusion: The risk of CVD is increased in patients with HNC treated by RT, and recent improvements in RT techniques may have contributed to the decreased risk of CVD. These results suggest that regular follow-up and appropriate screening for CVD should be required for patients with HNC.

Endoscopic Screening for Second Primary Tumors of the Esophagus Among Head and Neck Cancer Patients.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol's chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs.

A predictive model for advanced oropharyngeal cancer patients treated with chemoradiation.

BACKGROUND: To analyze clinical characteristics in the prediction of death within 1 year in advanced oropharyngeal cancer patients treated with chemoradiation. METHODS: One hundred forty-seven advanced oropharyngeal cancer patients who underwent curative-intent chemoradiation treatment were retrospectively enrolled. The pre-treatment clinical parameters including inflammatory markers were reviewed. RESULTS: The 1-year death rate for all patients was 29% [95% confidence interval (CI): 23-37%]. In multivariate logistic regression analysis, hemoglobulin (Hb) < 13.5 g/dl was an independent indicator of death within 1-year [Odds ratio (OR) 5.85, 95% CI 2.17-15.75, p < 0.001]. Systemic immune inflammation (SII) ≥ 1820 was also a significant factor for prediction of death within 1 year (OR 4.78, 95% CI 1.44-15.85, p = 0.011). We further used gander, age, Hb and SII to develop a nomogram to predict death within 1 year. The c-index of the model was 0.75 (95%CI 0.66-0.83). For patients with low nomogram score (< 14) versus high nomogram score (≥ 14), the 1-year and 2-year OS rates were 91 and 71% versus 53 and 29%, respectively. (p < 0.001). A difference in the disease persistence or recurrence rate between patients with high and low nomogram score was significant (73 and 28%, respectively; p < 0.001). CONCLUSIONS: The pre-treatment Hb < 13.5 g/dl and SII ≥ 1820 are associated with higher risks of death within 1-year in patients with advanced oropharyngeal cancers. Nomogram can aid in patient counseling and treatment modality adjustment. The development of a more effective treatment protocol for patients with high nomogram score will be essential.

Cardiac Function after Modern Radiation Therapy with Volumetric Modulated Arc Therapy or Helical Tomotherapy for Advanced Left-Breast Cancer Receiving Regional Nodal Irradiation.

BACKGROUND: Protecting cardiac function in patients with advanced left-breast cancer receiving radiation therapy (RT) with regional nodal irradiation (RNI) is an important issue. Modern RT techniques can limit cardiac exposure. The aim of this study was to explore the association be-tween cardiac dose and cardiac function. METHODS: Between 2017 and 2020, we retrospectively reviewed left-breast cancer patients who received adjuvant RT, including RNI with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT). Left ventricular ejection fraction (LVEF) was assessed by echocardiography before RT and 1 year after RT to detect any early deterioration in cardiac systolic function. RESULTS: A total of 30 eligible patients were enrolled. The median follow-up time from the initiation of RT was 3.9 years (range 0.6-5 years). Seventeen patients received VMAT, and the other 13 patients received HT. The median RT dose was 55 Gray (Gy), and the mean heart dose was 3.73 Gy (range 1.95-9.36 Gy). The median LVEF before and after RT was 68% and 68.5%, respectively. No obvious deterioration was found. There was no association between cardiac dose (mean heart dose, V5-V30) and LVEF (change in values or post-RT). CONCLUSIONS: For left-breast cancer patients undergoing RT with RNI, VMAT, or HT can be used to limit cardiac exposure. Cardiac function as evaluated by LVEF revealed no obvious deterioration after RT in our patients, and no association was found between cardiac dose and LVEF in those treated with either VMAT or HT in early cardiac surveillance.

Impact of Irradiation on the Pharmacokinetics and Biotransformation of Tamoxifen.

BACKGROUND: The optimal procedure for combining radiotherapy (RT) with tamoxifen treatment is controversial as RT may alter the pharmacokinetics and biotransformation of tamoxifen. The present study investigated this potential interaction by assessing the pharmacokinetics of tamoxifen during concurrent and sequential RT. METHOD: Plasma tamoxifen concentration was measured in rats with or without RT 2.0 Gy (RT2.0Gy) or 0.5 Gy (RT0.5Gy) with ultra-high-performance liquid chromatography-tandem mass spectrometry after tamoxifen administration (10 mg/kg, p.o., n = 6). Tamoxifen was either administered 1 h after RT (concurrent condition) or 24 h after RT (sequential condition). RESULTS: Pharmacokinetic data analysis demonstrated that the area under the curve (AUC) and half-life of tamoxifen were 2,004 ± 241 h ng/ml and 6.23 ± 1.21 h, respectively, after tamoxifen administration (10 mg/kg, p.o.). The respective conversion rate of 4-hydroxytamoxifen, N-desmethytamoxifen, and endoxifen for tamoxifen metabolism was 20%, 16%, and 5%. The AUC value of tamoxifen in the RT0.5Gy group was 1.5- to 1.7-fold higher than in the sham and RT2.0Gy groups. The relative bioavailability of tamoxifen at concurrent RT0.5Gy and RT2.0Gy groups ranged from 127% to 202% and from 71% to 152%, respectively. The magnitude of endoxifen, which converted from 4-hydroxytamoxifen and N-desmethyltamoxifen, increased 3- to 5-fold in the concurrent RT groups. By contrast, the AUC of tamoxifen decreased by roughly 24% in the sequential RT2.0Gy group. The conversion ratio of endoxifen was four times higher than that in the sequential RT2.0Gy group compared with rats not exposed to RT. CONCLUSION: The current study provides advanced pharmacokinetic data to confirm the interaction between RT and hormone therapy. Our findings indicate that RT facilitates the metabolism of tamoxifen to active metabolites and thus imply that combination RT-tamoxifen has potential benefits for the treatment of hormone-dependent breast cancer.

Nutritional status at diagnosis is prognostic for pharyngeal cancer patients: a retrospective study.

BACKGROUND: Malnutrition in head and neck cancer (HNC) patients is associated with increased morbidity and mortality. Several nutrition indicators have been reported to be related to the prognosis of HNC. However, the prognostic effect of these multiple nutrition factors in HNC is not well elucidated. The aim of this study was to evaluate the prognostic effect of these factors, including the novel hemoglobin, albumin, lymphocyte, and platelet (HALP) score, for pharyngeal cancers. MATERIAL AND METHODS: From 2008 to 2019, a total of 319 pharyngeal cancer patients were recruited. We collected adult patients with a diagnosis of nasopharyngeal carcinoma, oropharyngeal carcinoma and hypopharyngeal carcinoma. Patients who completed definite staging workup and treatment were selected for analysis. We traced nutritional and hematological parameters, including body mass index (BMI), albumin, and complete blood count, for survival analysis. RESULTS: We found that multiple nutritional markers, including BMI, hemoglobin, albumin, prognostic nutritional index (PNI), nutritional risk index (NRI) and HALP score, were important predictors for pharyngeal cancers in univariate Cox regression analysis. In multivariate analysis, we found that the HALP score was still an independent factor (HR: 1.62, 1.13-2.32 for overall survival [OS]) after adjusting of gender, age, cancer site, clinical stage, and BMI. The PNI was the most important independent factor for OS (HR: 3.12, 2.18-4.47) and cancer-specific survival (HR: 2.88, 1.88-4.41) in multivariate analysis. CONCLUSION: We found that multiple nutrition markers, including BMI, hemoglobin, albumin, PNI, NRI and HALP score, are important predictors for pharyngeal cancers. This is the first report confirming the prognostic effect of the HALP score for HNCs. Nutritional status at diagnosis should be given more attention in pharyngeal cancer patients.