Benefits of prophylactic percutaneous gastrostomy in patients with nasopharyngeal cancer receiving concurrent chemoradiotherapy: A multicenter analysis.

PURPOSE: Prophylactic percutaneous endoscopic gastrostomy (PPEG) is widely used for patients with head and neck cancer undergoing concurrent chemoradiation (CCRT). Nevertheless, the necessity of its use in patients with nasopharyngeal cancer (NPC) is uncertain. This study aimed to evaluate the benefits of PPEG on prevention of weight loss and treatment tolerance in patients with NPC receiving CCRT. MATERIALS AND METHODS: A retrospective multicenter chart review of 904 patients, 378 in the PPEG group and 526 in the non-PPEG group, was conducted. Baseline characteristics, weight loss, and treatment tolerance were analyzed and compared between the two groups. RESULTS: There was no significant difference in the mean baseline body mass index (BMI) between the groups. At the end of CCRT, no difference in weight loss was found between the 2 groups (non-PPEG group, 6.6%; PPEG group, 5.9%). Nonetheless, the subgroup analysis demonstrated that a baseline BMI < 18.5 kg/m2 (underweight) and non-intensity-modulated radiation therapy (IMRT) technique were independent factors associated with prevention of weight loss by PPEG. More patients in the PPEG group were able to complete planned cycles of chemotherapy (73.3% vs. 49.0%, P < .0001). CONCLUSION: Although the benefits of PPEG on prevention of weight loss were not observed for the entire cohort, we found a potentially protective effect of PPEG in some subgroups of patients. Additionally, PPEG significantly enhanced chemotherapy tolerance. Therefore, PPEG tube insertion should be strongly considered for patients with NPC receiving CCRT, particularly for underweight patients and those undergoing a non-IMRT technique.

Risk and impact of delayed renal impairment in patients with locally advanced head and neck squamous cell carcinoma receiving chemoradiotherapy with cisplatin.

BACKGROUND: An incidence of cisplatin-induced acute kidney injury (AKI) of 34% has been reported in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, delayed cisplatin-induced nephrotoxicity and long-term renal outcomes remain poorly studied. METHODS: Patients with LA-HNSCC who underwent definitive or postoperative cisplatin-based chemoradiotherapy (CRT) were included. Acute kidney disease (AKD) was defined as newly developed estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 for < 3 months, ≥ 35% decrease in eGFR, or > 50% increase in serum creatinine for <3 months from baseline. RESULTS: A total of 509 patients were analyzed. AKD and AKI occurred in 27.9% and 13.4% of patients, respectively. Most patients had primary prophylactic feeding tube (95%) and definitive CRT (83%). More AKD patients had an ECOG status of 0 (p = 0.017), diabetes (p = 0.044), and hypertension (p < 0.001). AKI, but not AKD, was significantly associated with cumulative cisplatin dose, delay, dose reduction, termination, and hospitalization during CRT. GFR percentage in patients with AKD declined significantly during CRT (- 36%), worsened at 3 months (- 39%), and had not recovered to baseline at 12 months after CRT (- 29%). Multivariate analysis identified ECOG status 0 and hypertension as significantly associated with the development of AKD. CONCLUSION: Almost one third of LA-HNSCC patients who underwent CRT with cisplatin developed AKD, and their eGFR did not recover to baseline even after 1 year. ECOG 0 and hypertension were associated with AKD. These findings may have been due to the physician's awareness of AKD and underestimation of its potential complications in fit patients.

Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with non-metastatic nasopharyngeal carcinoma: a multicenter analysis in Thailand.

BACKGROUND: Chemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for non-metastatic nasopharyngeal carcinoma (NPC). However, given most patients' inability to tolerate high CDs due to cisplatin-related toxicities, the optimal CD of cisplatin during CRT remains undetermined. METHODS: Patients with non-metastatic NPC who received CRT with cisplatin between 2007 and 2017 were identified through the Thai head and neck cancer multicenter database and then categorized according to cisplatin CD (mg/m2) received. All complications and cisplatin-related toxicities during CRT were recorded. RESULTS: We identified 779 non-metastatic NPC patients receiving low (≤150; n = 97), intermediate (151-250; n = 411), and high (> 250; n = 271) CDs of cisplatin. Low CD patients had significantly lower mean actual radiation dose (p < 0.001) and more radiotherapy delay (p = 0.010), while intermediate CD patients had the least hospitalization (p < 0.001). Overall, 39.3% of the patients experienced cisplatin-related toxicity, which was associated with poor overall survival (OS) (p = 0.001). Acute kidney injury was observed in 7% in all patients, which was highest among low CD patients (15.5%; p = 0.002). Intermediate CD patients had significantly longer median OS than the low and high groups (64 vs. 49.8 vs. 53.2, respectively; p = 0.015). Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with OS. CONCLUSION: CD of cisplatin during CRT was not an independent prognostic factor for OS. An intermediate CD induced minimal toxicity without compromising survival and should be considered the optimal CD. Nonetheless, a randomized phase 3 study evaluating the optimal CD of cisplatin is warranted.

Clinical outcome of postoperative radiotherapy with or without chemotherapy in adult glioblastoma multiforme in Ramathibodi Hospital: a retrospective study.

OBJECTIVE: To identify the treatment outcome of glioblastoma multiforme (GBM) in Ramathibodi Hospital from overall survival rate and related prognostic factors. MATERIAL AND METHOD: Medical records of patients with histological diagnosis of GBM treated at Radiation Oncology Division, Radiology Department, Ramathibodi Hospital between 2000 and 2010 were reviewed and available data extracted for evaluation of treatment outcome. RESULTS: There were 47 patients with mean age at diagnosis of 51.9 years (range from 18 to 82 years). Surgery (partial 76.6%, total 12.8%, and biopsy 10.6%) followed by postoperative radiotherapy (mean dose 52 gray) was the treatment of choice with or without concurrent and adjuvant Temozolomide (TMZ). With median follow-up time of 0.9 years, the median survival of the patients was 2.1 years (95% CI 1.08-7.36), whereas one and two-year overall survival rates were 78.0% and 57.8%, respectively. In univariate analysis, persistent neurological deficit after surgery and presenting symptom of visual disturbance were identified to lower overall survival while multivariate analysis, younger age, and higher radiation dose were identified as favorable prognostic factors to improve overall survival. Re-surgery or re-irradiation in some selected cases of recurrent or progressive disease was considered as a choice for palliative treatment. CONCLUSION: Proper management of GBM patient was surgical removal and postoperative radiotherapy with or without chemotherapy. Proper palliative treatment modality was considered in selected cases of recurrent or progressive disease.

Early recurrence, time-to-recurrence, and recurrence patterns: Assessing their impact on survival outcomes in head and neck squamous cell carcinoma (R/M-HNSCC) patients treated with first line platinum-based chemotherapy.

BACKGROUND: R/M-HNSCC patients typically receive 1L platinum-based chemotherapy with pembrolizumab or cetuximab. However, the outcomes for patients with early recurrence (<6 months) remain unclear due to their exclusion from most 1L studies. This study aimed to assess the impact of time-to-recurrence intervals (TTRI) and recurrence patterns on the survival of R/M-HNSCC patients. METHODS: We identified non-curable R/M-HNSCC patients at our institution from 1/2008 through 6/2020. We analyzed the outcomes of early recurrent patients who received 1L systemic treatment, with different TTRIs and recurrence patterns. RESULTS: Our study included 234 eligible patients. The majority (47%) experienced early recurrence (<6 months), while 22%, 20%, and 11% had recurrences at 6-12 months, >12 months, and de novo metastasis, respectively. The platinum-based regimen was the most commonly used chemotherapy (86%), with cetuximab and immunotherapy utilized in 3% and 5% of cases, respectively. Significant differences in PFS and OS were observed among TTRI groups. For patients with early recurrence, both platinum-doublet and monotherapy treatments significantly improved OS. Locoregional recurrence (47%) was the most common, followed by distant metastasis (22%) and both (20%). Recurrence patterns were significantly associated with OS but not with PFS. In multivariate analysis, TTRI ≥12 months significantly correlated with improved PFS (HR 0.51; p = 0.004) and OS (HR 0.58; p = 0.009), whereas recurrent pattern did not. CONCLUSION: TTRI significantly influenced the survival, while recurrence patterns did not. In our study, the retrospective design limited our ability to definitively establish whether early recurrent R/M-HNSCC patients would benefit more from platinum-doublet. Despite poor prognosis, early recurrent patients benefited from 1L systemic treatments. Given the variation in prognoses, TTRI should be considered a stratification factor in future clinical trials.

The Investigating Image Registration Accuracy and Contour Propagation for Adaptive Radiotherapy Purposes in Line with the Task Group No. 132 Recommendation.

Purpose: Image registration is a crucial component of the adaptive radiotherapy workflow. This study investigates the accuracy of the deformable image registration (DIR) and contour propagation features of SmartAdapt, an application in the Eclipse treatment planning system (TPS) version 16.1. Materials and Methods: The registration accuracy was validated using the Task Group No. 132 (TG-132) virtual phantom, which features contour evaluation and landmark analysis based on the quantitative criteria recommended in the American Association of Physicists in Medicine TG-132 report. The target registration error, Dice similarity coefficient (DSC), and center of mass displacement were used as quantitative validation metrics. The performance of the contour propagation feature was evaluated using clinical datasets (head and neck, pelvis, and chest) and an additional four-dimensional computed tomography (CT) dataset from TG-132. The primary planning and the second CT images were appropriately registered and deformed. The DSC was used to find the volume overlapping between the deformed contours and the radiation oncologist (RO)-drawn contour. The clinical value of the DIR-generated structure was reviewed and scored by an experienced RO to make a qualitative assessment. Results: The registration accuracy fell within the specified tolerances. SmartAdapt exhibited a reasonably propagated contour for the chest and head-and-neck regions, with DSC values of 0.80 for organs at risk. Misregistration is frequently observed in the pelvic region, which is specified as a low-contrast region. However, 78% of structures required no modification or minor modification, demonstrating good agreement between contour comparison and the qualitative analysis. Conclusions: SmartAdapt has adequate efficiency for image registration and contour propagation for adaptive purposes in various anatomical sites. However, there should be concern about its performance in regions with low contrast and small volumes.

A Phase I Study of the CDK4/6 Inhibitor Palbociclib in Combination with Cetuximab and Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

PURPOSE: Palbociclib, a cyclin D kinase 4 (CDK4)/6 inhibitor, has shown radiosensitizing effects in preclinical studies. There is a strong rationale for adding palbociclib to cetuximab and radiotherapy in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), especially in p16-negative HNSCC. PATIENTS AND METHODS: We conducted a phase I dose-escalation study (NCT03024489) using a classical 3+3 design to determine safety, tolerability, and MTD of palbociclib, cetuximab, and intensity-modulated radiotherapy (IMRT) combination. At the recommended phase II dose (RP2D), additional p16-negative patients were enrolled. RESULTS: Twenty-seven patients with LA-HNSCC (13 in dose escalation, 14 in expansion) with oropharyngeal (41%) and hypopharyngeal (30%) cancers were enrolled. The MTD was not reached, and the RP2D of palbociclib was established at the full standard palbociclib dose of 125 mg/day for 21 days per cycle, administered for two cycles during IMRT. The most common grade 3-4 toxicities were mucositis (59%), radiation dermatitis (22%), and neutropenia (22%), with a febrile neutropenia rate of 7%. Common genomic alterations included mutations in TP53 (57%), GNAQ (35%), and PIK3CA (17%), and copy-number gains in CCND1 (22%), CCND2 (9%), and EGFR (9%). Overall, p16 expression was positive in 15% of patients. No correlation was observed between p16 status, genomic alterations, and preliminary efficacy. The objective response rate was 84%. The rates for 2-year locoregional control, event-free survival, and overall survival were 73%, 48%, and 71%, respectively. CONCLUSIONS: The palbociclib, cetuximab, and IMRT combination was well tolerated. The RP2D was established, while no MTD was determined. The regimen demonstrated promising preliminary efficacy, suggesting further investigation is warranted in patients with cisplatin-ineligible p16/human papilloma virus-unrelated LA-HNSCC.

Preliminary experience of CyberKnife treatment of lung metastasis: the question about real clinical benefit.

OBJECTIVE: Evaluate the effectiveness of radiotherapy plan and physical parameters including local tumor response and clinical outcome of lung metastasis in patients who received CyberKnife treatment at Ramathibodi Hospital. MATERIAL AND METHOD: Six cases with twenty lesions of lung metastasis patients were evaluated for tumor response after having received CyberKnife treatment. The prescribed radiation dose was calculated approximately to biological equivalent dose (BED) around 60 to 100 gray (Gyz). The response of each lesion to treatment was evaluated from roentgenographic study during follow-up period along with adverse event, status of patients, and disease. RESULTS: At the third month after treatment, roentgenographic partial response (PR, 50% decrease in size) was demonstrated in eight lesions and stable disease (SD, unchanged size) in eight lesions with no complete response (CR, disappearance of tumor) detected. Progressive disease (PD, 25% increase in size) of six treated lesions was detected during the follow-up period. At the time of report, two patients were alive and still received palliative chemotherapy, two patients died from uncontrolled progressive metastases and failed palliative chemotherapy, and two patients lost follow-up after progressive metastases with unknown surviving status. No severe adverse event was observed. The treatment planning parameters demonstrated borderline of radiation dose homogeneity, and conformality coverage of the target volume. CONCLUSION: This preliminary report aimed to provide the idea of choosing the appropriate lung metastasis patient to receive CyberKnife treatment that must strictly clarify the real clinical benefit of each selected case to achieve the best outcome from this special treatment procedure.

Evolving role of novel radiosensitizers and immune checkpoint inhibitors in (chemo)radiotherapy of locally advanced head and neck squamous cell carcinoma.

Chemoradiotherapy (CRT) remains the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), based on numerous randomized controlled trials and meta-analyses demonstrating that CRT improved locoregional control and overall survival. Achieving locoregional control is a crucial outcome for the treatment of HNSCC, as it directly affects patient quality of life and survival. Cisplatin is the recommended standard-of-care radiosensitizing agent for LA-HNSCC patients undergoing CRT, whereas cetuximab-radiotherapy is reserved for cisplatin-ineligible patients. Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of recurrent or metastatic HNSCC. However, the combination of ICIs with standard-of-care radiotherapy or chemoradiotherapy in LA-HNSCC has not demonstrated significant improvement in survivals. Over the past few decades, significant advancements in radiotherapy techniques have allowed for more precise and effective radiation delivery while minimizing toxicity to surrounding normal tissues. These advances have led to improved treatment outcomes and quality of life for patients with LA-HNSCC. Despite these advancements, the development of novel radiosensitizing agents remains an unmet need. This review discusses the mechanism of radiotherapy and its impact on the immune system. We summarize the latest clinical development of novel radiosensitizing agents, such as SMAC mimetics, DDR pathway inhibitors, and CDK4/6 inhibitor. We also elucidate the emerging evidence of combining ICIs with radiotherapy or chemoradiotherapy in curative settings for LA-HNSCC, using both concurrent and sequential approaches. Lastly, we discuss the future direction of systemic therapy in combination with radiotherapy in treatment for LA-HNSCC.

Real-world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis.

BACKGROUND: Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA-NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA-NPC patients. METHODS: Patients with LA-NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan-Meier method, and compared by the log-rank test. A p-value of <0.05 was considered statistically significant. RESULTS: A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p < 0.001), smoking (p = 0.003), more comorbidity (p = 0.014), kidney disease (p = 0.016), and lower baseline creatinine clearance (p < 0.001). Intensity-modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p < 0.001). Patients who received carboplatin were associated with delay (p = 0.049) and hospitalization (p = 0.006), whereas cisplatin CCRT had more dose reduction (p = 0.001). Patients treated with cisplatin had CCRT interruption from grade 3-4 mucositis (p = 0.019) more than carboplatin, whereas carboplatin had more grade 3-4 thrombocytopenia (p < 0.001). The 5-year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p = 0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence-free survival in multivariate analysis. CONCLUSIONS: Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real-world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin-ineligible patients with LA-NPC treated with CCRT.

Preliminary experience of CyberKnife treatment of primary non-small cell lung cancer.

OBJECTIVE: Provide the effectiveness of treatment protocol, radiotherapy plan, technique, and early clinical results of inoperable primary non-small cell lung cancer (NSCLC) in patients who received CyberKnife treatment at Ramathibodi Hospital. MATERIAL AND METHOD: Six cases of inoperable primary NSCLC patients were evaluated for tumor response after having received CyberKnife treatment. The prescribed radiation dose was 45 gray (Gy) in three consecutive fractions for peripherally located tumor and 50 Gy in five fractions within two weeks for centrally located tumor (biological equivalent dose, BED, 112.5 Gy 10, and 100 Gy 10, respectively). The response to treatment was evaluated from roentgenographic study during follow-up period along with clinical outcome and adverse event. RESULTS: Overall response after the treatment was demonstrated in five cases with roentgenographic complete response (CR, disappearance of tumor) and partial response (PR, 50% decrease in size) in two and three cases, respectively without any severe adverse event. The treatment planning parameters demonstrated the effectiveness of radiation dose homogeneity and conformity coverage of the target volume. CONCLUSION: This preliminary report has provided the effectiveness of treatment plan and local tumor controlled without severe adverse event for primary inoperable NSCLC patients receiving CyberKnife treatment.

Radiomic and Dosiomic Features for the Prediction of Radiation Pneumonitis Across Esophageal Cancer and Lung Cancer.

PURPOSE: The aim was to investigate the advantages of dosiomic and radiomic features over traditional dose-volume histogram (DVH) features for predicting the development of radiation pneumonitis (RP), to validate the generalizability of dosiomic and radiomic features by using features selected from an esophageal cancer dataset and to use these features with a lung cancer dataset. MATERIALS AND METHODS: A dataset containing 101 patients with esophageal cancer and 93 patients with lung cancer was included in this study. DVH and dosiomic features were extracted from 3D dose distributions. Radiomic features were extracted from pretreatment CT images. Feature selection was performed using only the esophageal cancer dataset. Four predictive models for RP (DVH, dosiomic, radiomic and dosiomic + radiomic models) were compared on the esophageal cancer dataset. We further used a lung cancer dataset for the external validation of the selected dosiomic and radiomic features from the esophageal cancer dataset. The performance of the predictive models was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROCAUC) and the AUC of the precision recall curve (PRAUC) metrics. RESULT: The ROCAUCs and PRAUCs of the DVH, dosiomic, radiomic and dosiomic + radiomic models on esophageal cancer dataset were 0.67 ± 0.11 and 0.75 ± 0.10, 0.71 ± 0.10 and 0.77 ± 0.09, 0.71 ± 0.11 and 0.79 ± 0.09, and 0.75 ± 0.10 and 0.81 ± 0.09, respectively. The predictive performance of the dosiomic- and radiomic-based models was significantly higher than that of the DVH-based model with respect to esophageal cancer. The ROCAUCs and PRAUCs of the DVH, dosiomic, radiomic and dosiomic + radiomic models on the lung cancer dataset were 0.64 ± 0.18 and 0.37 ± 0.20, 0.67 ± 0.17 and 0.37 ± 0.20, 0.67 ± 0.16 and 0.45 ± 0.23, and 0.68 ± 0.16 and 0.44 ± 0.22, respectively. On the lung cancer dataset, the predictive performance of the radiomic and dosiomic + radiomic models was significantly higher than that of the DVH-based model. However, the PRAUC of the dosiomic-based model showed no significant difference relative to the corresponding RP prediction performance on the lung cancer dataset. CONCLUSION: The results suggested that dosiomic and CT radiomic features could improve RP prediction in thoracic radiotherapy. Dosiomic and radiomic feature knowledge might be transferrable from esophageal cancer to lung cancer.

Impact of Weight Loss on Patients with Locally Advanced Esophageal and Esophagogastric Junction Cancers Treated with Chemoradiotherapy.

INTRODUCTION: Malnutrition and weight loss are commonly observed in patient with esophageal and esophagogastric junction (EGJ) cancers. Chemoradiotherapy (CRT) is a mainstay of treatment for locally advanced esophageal and EGJ cancers. Impact of weight loss on patients with treated with CRT was not well studied. METHODS: Patients with locally advanced esophageal and EGJ cancer who received CRT were identified in our institutional database and allocated into low (LWL) and high (HWL) weight loss groups. HWL was defined as weight loss >5% of baseline during CRT. RESULTS: A total of 167 patients were underwent definitive (n=89) or preoperative (n=78) CRT, respectively. HWL was observed in 46% and 55% of patients treated with definitive and preoperative CRT, respectively. Cisplatin/5FU regimen used during CRT was a significant predictive factor for weight loss in multivariate analysis (OR 2.07, 95% CI 1.09-3.94; p=0.026). In the definitive CRT group, patients in the HWL group experienced significantly worse overall survival than those in the LWL group (1.2 years vs 1.95 years; p=0.003). Multivariate analysis revealed that baseline albumin (>3.0 g/dL) was significantly associated with longer OS of definitive CRT patients (HR 2.15, 95% CI 1.1-4.19; p=0.024). Tolerability and toxicities during CRT were not statistically different between groups. CONCLUSION: Significant weight loss during CRT was frequently observed in patients with locally advanced esophageal and EGJ cancers. Baseline hypoalbuminemia was an independent prognostic factor for OS in patients treated with definitive CRT. Nutritional support before and during treatment should be considered to potentially improve patients' outcomes.
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Can Radiation Therapy Quality Assurance Improve Nasopharyngeal Cancer Outcomes in Low- and Middle-Income Countries: Reporting the First Phase of a Prospective International Atomic Energy Agency Study.

PURPOSE: Most new nasopharyngeal cancer cases occur in low-income and middle-income countries, and these patients experience poorer overall survival than that of new nasopharyngeal cancer cases in high-income countries. The goal of this research project is to determine whether the introduction of a radiation therapy quality assurance program can ultimately improve outcomes for nasopharyngeal cancer patients in lower-income and middle-income countries. This study reports the results of the first phase of the International Atomic Energy Agency Coordinated Research Project (325-E3-TM-47712). METHODS AND MATERIALS: This prospective study has 2 phases. Phase 1 is a survey of radiation therapy resources, patient characteristics and treatment, and results of radiation therapy quality assurance performed by the expert panel. An educational workshop reviewing phase 1 results for each center was completed before accrual of patients for phase 2. The ultimate aim of the study is to compare the first and second cohort of patients to see if quality assurance can result in fewer major protocol deviations and a 15% improvement in patients' 3-year progression-free survival. RESULTS: Of 14 participating centers, 13 (93%) had computed tomography simulators and linear accelerators (LINAC) with intensity modulated radiation therapy (IMRT) capacity, median 3 LINAC (range, 1-13), and median 10 radiation oncologists (range, 5-51). The annual number of nasopharyngeal cancer cases irradiated was median 54 (range, 10-627). Five of 14 centers (36%) had no local radiation therapy quality assurance. For the current phase 1 study, 134 patients were evaluated, 82.1% had MRI staging, 99.3% had metastatic workup, 65.6% undifferentiated histology, 51% stage 3 and 49% stage 4. Radiation therapy quality assurance revealed 81 (60.4%) of 134 patients had major protocol violations in gross tumor volume and high dose planning target volume contours and/or dosimetry, 28.4% patients had borderline plans, 15 (11.2%) acceptable, and only 6 (4.2%) had inevitable compromise due to tumor extent. CONCLUSIONS: This is the first International Atomic Energy Agency study to address the fundamental issue of treatment quality rather than altered treatment regimens. The high rate of unacceptable radiation therapy plans is a major concern, and we hope phase 2 will show a significant reduction and improved patient outcomes.

Characteristics and Impact of HPV-Associated p16 Expression on Head and Neck Squamous Cell Carcinoma in Thai Patients.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy in Asia. Infection by human papilloma virus (HPV) has been recognized as an etiological risk for HNSCC, especially oropharyngeal region. While the association between HPV and HNSCC has been well evaluated in Western countries, only a few investigated the HPV-associated HNSCC in Southeast Asia. This study evaluated the prevalence, the characteristics, and the impact of HPV on the treatment outcomes in Thai HNSCC patients. METHODS: Non-nasopharyngeal HNSCC patients treated at Ramathibodi Hospital during 2007-2013 were identified through the cancer registry database. Baseline patient, treatment data and survivals were retrospectively reviewed. The formalin-fixed paraffin-embedded (FFPE) tissue sections were retrieved for p16 analysis. The HPV status was determined by p16 immunohistochemistry. The survival outcomes were analyzed in cases which p16 status was confirmed. RESULTS: Total of 200 FFPE tissues of HNSCC patients was evaluated for p16 expression. Positive p16 status was observed in 24 cases (12%); majority of p16-positive were men (20:4 cases). The oropharynx (37.9%) was the most common site found in p16-positive while oral cavity (3.2%) was the least common site. Interestingly, 66.7% of p16-positive were former/current smokers, and 70.8% of this subgroup was categorized as clinical AJCC stage III-IV. The p16-positive HNSCC was significantly superior in 5-year overall survival [5-yrs OS 63% vs. 40%, p=0.03], 5-year disease-free survival [5-yrs DFS 61% vs. 36%, p=0.03] and in 5-year locoregional relapse-free survival [5-yrs LRFS 93% vs. 68%, p=0.018] when compared with p16-negative. CONCLUSIONS: In comparison to the results from the Western countries, the prevalence of HPV-related HNSCC in Thai patients was less, and differences in some characteristics were observed. Nevertheless, improvement in OS, DFS and LRFS were observed in p16-positive patients. Our analyses suggested that p16 status is also a strong prognostic marker for HNSCC patients in Thailand.

Characteristics and impact of programmed death-ligand 1 expression, CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma.

BACKGROUND: No predictive biomarker of immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) has been well established. The impact of programmed death-ligand 1 (PD-L1) expression, CD8+ tumor-infiltrating lymphocytes (TILs), and p16 status in HNSCC is unclear and may vary according to ethnicity. METHODS: HNSCC patients treated between 2007 and 2013 were reviewed. Archival tissues were retrieved for PD-L1, CD8+ TILs, and p16 analyses. PD-L1 expression was evaluated by using the validated SP142 assay on the VENTANA platform. CD8+ TILs were defined by using semiquantitative scoring. RESULTS: A total of 203 patients were analyzed. PD-L1 expression was observed in 80% of patients and was significantly associated with older age (P < 0.001). A high CD8+ TIL score (≥ 6) was significantly associated with never-smoking (P = 0.020), oral cavity cancer (P < 0.001), and stage M0 at presentation (P = 0.025). The p16 status was positive in 12% of patients. Patients with a high TIL score had a significantly longer OS (P = 0.032). Patients with PD-L1 expression of 1-49% and ≥ 50% were associated with a significantly shorter OS compared with those with PD-L1 < 1% (P = 0.027 and P = 0.011, respectively). Multivariate analysis showed that PD-L1 ≥ 50% was significantly associated with a poor OS. (HR 2.98 [95% CI 1.2-7.39]; P = 0.019.) CONCLUSIONS: A high prevalence of PD-L1 expression was observed in HNSCC using the validated SP142 assay. PD-L1 expression was associated with older age, while highly PD-L1 expression (≥ 50%) was an independent prognostic factor for poor OS in anti-PD1/PD-L1 untreated HNSCC patients.

Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

OBJECTIVES: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients. MATERIALS AND METHODS: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated. RESULTS: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival. CONCLUSIONS: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored.

Uncommon response of cisplatin and etoposide for treatment of advanced medullary thyroid carcinoma.

Systemic treatment of Medullary thyroid carcinoma (MTC) is currently limited to the use of a tyrosine kinase inhibitor. Cytotoxic chemotherapy is not routinely recommended in the earlier lines of treatment due to the lack of efficacy. We describe a patient with locally advanced MTC who had an uncommon response to cisplatin and etoposide.

Tolerability and efficacy of concurrent chemoradiotherapy comparing carboplatin/paclitaxel versus platinum/5-FU regimen for locally advanced esophageal and esophagogastric junction cancers.

Platinum/5-fluorouracil (PF) is commonly used for chemoradiotherapy (CRT) for locally advanced esophageal and esophagogastric junction (EGJ) cancers. Weekly carboplatin and paclitaxel (CP) regimen for preoperative CRT has increased in popularity due to its potentially less toxicity. We retrospectively compared the tolerability and efficacy of these regimens. Patients with esophageal and EGJ squamous cell carcinoma (SCC) or adenocarcinoma who received CRT with curative intent were included. Safety and tolerability during CRT were evaluated using the CTCAE version 4.0. Efficacy was analyzed using pathologic complete response, disease-free survival, and overall survival. One hundred and twenty-four patients were eligible for analysis (CP = 64, PF = 60). Most patients had esophageal cancer (97%) with SCC histology (91%). Preoperative CRT was planned for 43% of patients in the CP group and 34% in the PF group (p = 0.306). The relative dose intensities of cisplatin (67.0%) and 5-fluorouracil (81.4%) were lower than those of carboplatin (86.6%) and paclitaxel (86.2%). No difference in the radiotherapy dose, hospitalization, interruption, or termination was observed between the groups. Dose reduction of chemotherapy was more frequent in the CP group (38 vs. 19%; p = 0.015). Febrile neutropenia was more frequent in the PF group (8 vs. 0%; p = 0.058). All-grade nausea/vomiting was lower in the CP group (20 vs. 38%; p = 0.032). Efficacy was comparable between both regimens. In the multivariate analysis, the CRT regimen was not a significant predictor of survival. The CP regimen had less toxicity than the PF regimen, while efficacy was comparable. A large prospective randomized study is warranted to confirm these results.

The Clinical Outcome of Hypofractionated Stereotactic Radiotherapy With CyberKnife Robotic Radiosurgery for Perioptic Pituitary Adenoma.

Stereotactic radiation technique including single fraction radiosurgery and conventional fractionated stereotactic radiotherapy is widely reported as an effective treatment of pituitary adenomas. Because of the restricted radiation tolerance dose of the optic pathway, single fraction radiosurgery has been accepted for small tumor located far away from the optic apparatus, while fractionated stereotactic radiotherapy may be suitable for larger tumor located close to the optic pathway. More recently, hypofractionated stereotactic radiotherapy has become an alternative treatment option that provides high rate of tumor control and visual preservation for the perioptic lesions within 2 to 3 mm of the optic pathway. The objective of the study was to analyze the clinical outcomes of perioptic pituitary adenomas treated with hypofractionated stereotactic radiotherapy. From 2009 to 2012, 40 patients with perioptic pituitary adenoma were treated with CyberKnife robotic radiosurgery. The median tumor volume was 3.35 cm3 (range, 0.82-25.86 cm3). The median prescribed dose was 25 Gy (range, 20-28 Gy) in 5 fractions (range, 3-5). After the median follow-up time of 38.5 months (range, 14-71 months), 1 (2.5%) patient with prolactinoma had tumor enlargement, 31 (77.5%) were stable, and the remaining 8 (20%) tumors were smaller in size. No patient's vision deteriorated after hypofractionated stereotactic radiotherapy. Hormone normalization was observed in 7 (54%) of 13 patients. No newly developed hypopituitarism was detected in our study. These data confirmed that hypofractionated stereotactic radiotherapy achieved high rates of tumor control and visual preservation. Because of the shorter duration of treatment, it may be preferable to use hypofractionated stereotactic radiotherapy over fractionated stereotactic radiotherapy for selected pituitary adenomas immediately adjacent to the optic apparatus.