Perihippocampal failure after hippocampal-avoidance brain radiotherapy in small cell lung cancer patients: Cases report and literature review.

RATIONALE: Brain metastasis is a major concern, and may occur in roughly 50% of patients during the clinical course of small cell lung cancer (SCLC). Because prophylactic cranial irradiation reduces the incidence of brain metastases and improves overall survival, prophylactic cranial irradiation is recommended for SCLC patients without distant metastases or an extensive stage and have responded well to systemic therapy. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) is preferred to preserve hippocampal function while minimizing negative cognitive effects. PATIENT CONCERNS: Reducing the dose delivered to the hippocampus below the therapeutic brain dose may increase the risk of hippocampal progression; thus, HA-WBRT may be associated with a risk of perihippocampal recurrence. DIAGNOSIS: Three patients with SCLC received HA-WBRT and developed intracranial failure during clinical follow-up; 3 relapsed with intracranial failure in the perihippocampal region after 12, 13, and 7 months, respectively. INTERVENTION AND OUTCOMES: Compared to the therapeutic brain dose of cases and the underdose region around the HA region, we matched MRI scans of intracranial failure and previous planning scans of simulation and found a deviation of the underdosed region within the perihippocampal failure of approximately 55% to 63%. LESSONS: Perihippocampal failure is a rare clinical outcome in SCLC patients following HA-WBRT. Perihippocampal failure could be caused by an underdose of radiation or by the aggressiveness of the cancer itself. More research into this topic is encouraged.

The role of adjuvant radiotherapy for intracranial malignant meningiomas: analysis of a nationwide database.

PURPOSE: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. METHODS: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. CONCLUSION: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.

Comparison of healthcare utilization and life-sustaining interventions between patients with glioblastoma receiving palliative care or not: A population-based study.

BACKGROUND: Palliative care has historically been under-utilized in patients with glioblastoma. Furthermore, literature on the utilization of healthcare and life-sustaining interventions during the late-stage of glioblastoma has been limited. AIM: To identify and compare healthcare utilization and life-sustaining interventions between patients with glioblastoma who received palliative care and who did not based on patients identified retrospectively from Taiwan Cancer Registry between January 2007 and December 2017. DESIGN: In this study, palliative care was defined on the basis of claims submitted to the National Health Insurance, which has a specific code for it. Variables included demographic characteristics, the utilization of healthcare services, and invasive life-sustaining interventions. SETTING/PARTICIPANTS: Of the 1994 patients with glioblastoma identified, 1784 fulfilled the inclusion criteria, 613 (34%) of whom received palliative care. RESULTS: The survival of patients with glioblastoma under palliative care was significantly longer than that of those without palliative care. Those without palliative care had significantly more frequent intensive care unit admissions and a longer cumulative length of intensive care unit stay. Regarding cardiopulmonary or respiratory treatments, patients without palliative care had significantly more invasive interventions than those with palliative care. Patients receiving palliative care had significantly lower odds than those without life-sustaining interventions. CONCLUSIONS: Our retrospective analysis reveals that glioblastoma patients without palliative care had greater odds of receiving life-sustaining treatments within 1 year before their death, although no gains in survival as compared to those that received palliative care. These findings highlight the urgent need for palliative care in caring for patients with glioblastoma.

Treatment outcomes of primary surgery versus chemoradiotherapy for T4 oropharyngeal cancers.

Concurrent chemoradiotherapy (CCRT) has been the standard of care for locally advanced diseases regardless of human papillomavirus infection status. Other treatment options include surgery followed by adjuvant therapy and induction chemotherapy followed by CCRT or radiotherapy. However, for locally advanced T4 laryngeal or hypopharyngeal diseases, surgery is preferred over CCRT. Given the improvement in the functional outcomes of surgery, examining the oncologic outcomes in OPSCC patients is critical. This study aimed to determine whether differences in overall survival (OS) exist between surgery and CCRT. Oropharyngeal cancer patients included in the cancer registry of our hospital from January 2014 to December 2018 were retrospectively analyzed. Patients with T4 disease who underwent curative treatment were identified. In this study, the primary and secondary outcomes were OS and disease-free survival (DFS), respectively. Potential confounding factors were also evaluated. Details regarding recurrence pattern were listed. From 2014 to 2018, 74 newly diagnosed oropharyngeal cancer patients were identified from our cancer registry database, 60 of whom satisfied our inclusion criteria. Our findings showed an OS of 25.5 months and DFS of 17.5 months. No significant difference in both of OS and DFS were observed between the surgery and CCRT cohorts. Sex, stage, second primary cancer, IC, and primary treatment were not correlated with DFS. Male sex was the only significant factor identified, with an HR of 0.2 for OS (95% confidence interval, 0.06-0.71). No significant difference in both OS and DFS were observed between the CCRT and surgery cohorts. CCRT remains the standard of care for locally advanced disease.

Perihippocampal failure after hippocampal-avoidance whole-brain radiotherapy in cancer patients with brain metastases: Results of a retrospective analysis.

ABSTRACT: Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged.

Retrospective analysis of adjuvant radiotherapy in oral cavity or oropharyngeal cancer: Feasibility of omitting lower-neck irradiation.

OBJECTIVES: Adjuvant radiotherapy is the standard of care in locally advanced head and neck cancers. The radiation field is correlated with the surgical field in the adjuvant radiotherapy setting; therefore, tailoring the irradiation field is reasonable. MATERIALS AND METHODS: We retrospectively analyzed patients with oral cavity and oropharyngeal cancers included in the cancer registry between 2015 and 2019 in the study hospital. Patients who underwent whole-neck irradiation (WNI) were compared with those who underwent lower-neck-sparing (LNS) irradiation. RESULTS: A total of 167 patients with oral cavity and oropharyngeal cancers were included in the study. Cancer recurrence was recorded in 33% of the patients. The rate of recurrence of oral cavity and oropharyngeal cancer at neck level IV was 8%. The 2-year incidence of level IV recurrence was lower in the WNI group than in the LNS group (2% vs. 10%; p = 0.04). The 2-year disease-free survival rates were 75% and 63% in the WNI and LNS groups, respectively (p = 0.08). CONCLUSION: The rate of level IV recurrence was higher in the LNS group than in the WNI group. Trends of improvement in disease-free survival with lower-neck irradiation suggested that it is premature to consider LNS irradiation as daily practice in patients with oral cavity and oropharyngeal cancer.

Epidemiologic Features, Survival, and Prognostic Factors Among Patients With Different Histologic Variants of Glioblastoma: Analysis of a Nationwide Database.

Background: Glioblastoma (GBM) is the most common primary intracranial malignancy. Previous studies found incidence of GBM varies substantially by age, sex, race and ethnicity, and survival also varies by country, ethnicity, and treatment. Gliosarcoma (GSM) and giant cell glioblastoma (GC-GBM) are different histologic variants of GBM with distinct clinico-pathologic entities. We conducted a study to compare epidemiology, survival, and prognostic factors among the three. Methods: We identified GBM patients diagnosed between 2000 and 2016 using the Taiwan Cancer Registry and followed them using the death registry. Survival was compared among conventional GBM and two histologic variants. The potential confounding factors evaluated in this study included registered year, age, sex, and treatment modality (resection, radiotherapy, and chemotherapy). Results: We enrolled 3,895 patients, including 3,732 (95.8%) with conventional GBM, 102 (2.6%) with GSM, and 61 (1.6%) with GC-GBM. GC-GBM patients had younger mean age at diagnosis (49.5 years) than conventional GBM patients (58.7 years) and GSM patients (61.3 years) (p < 0.01). The three groups had similar sex distributions (p = 0.29). GC-GBM had a longer median survival [18.5, 95% confidence interval (CI): 15.8-25.3 months] than conventional GBM (12.5, 95%CI: 12.0-13.0 months) and GSM (12.8, 95%CI: 9.2-16.2 months), and the differences in overall survival did not attain statistical significance (p = 0.08, log-rank test). In univariate analysis, GC-GBM had better survival than conventional GBM, but the hazard ratio (0.91) did not reach statistical significance (95%CI: 0.69-1.20) in the multivariate analysis. Young ages (≤ 40 years), female sex, resection, radiotherapy, and chemotherapy were factors associated with better survival in overall GBMs. In subtype analyses, these factors remained statistically significant for conventional GBM, as well as radiotherapy for GSM. Conclusion: Our analysis found conventional GBM and its variants shared similar poor survival. Factors with age ≤ 40 years, female sex, resection, radiotherapy, and chemotherapy were associated with better prognosis in conventional GBM patients.

Survival of glioblastoma treated with a moderately escalated radiation dose-Results of a retrospective analysis.

Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors and typically tends to recur locally just adjacent to the original tumor site following surgical resection and adjuvant radiotherapy. We conducted a study to evaluate the survival outcomes between a standard dose (≤ 60 Gy) and moderate radiation dose escalation (>60 Gy), and to identify prognostic factors for GBM. We retrospectively reviewed the medical records of primary GBM patients diagnosed between 2005 and 2016 in two referral hospitals in Taiwan. They were identified from the cancer registry database and followed up from the date of diagnosis to October 2018. The progression-free survival (PFS) and overall survival (OS) were compared between the two dose groups, and independent factors for survival were analyzed through Cox proportional hazard model. We also affirmed the results using Cox regression with least absolute shrinkage and selection operator (LASSO) approach. From our cancer registry database, 142 GBM patients were identified, and 84 of them fit the inclusion criteria. Of the 84 patients, 52 (62%) were males. The radiation dose ranged from 50.0 Gy to 66.6 Gy, but their treatment volumes were similar to the others. Fifteen (18%) patients received an escalated dose boost >60.0 Gy. The escalated group had a longer median PFS (15.4 vs. 7.9 months, p = 0.01 for log-rank test), and a longer median OS was also longer in the escalation group (33.8 vs. 12.5 months, p <0.001) than the reference group. Following a multivariate analysis, the escalated dose was identified as a significant predictor for good prognosis (PFS: hazard ratio [HR] = 0.48, 95% confidence interval [95%CI]: 0.23-0.98; OS: HR = 0.40, 95%CI: 0.21-0.78). Using the LASSO approach, we found age > 70 (HR = 1.55), diagnosis after 2010 (HR = 1.42), and a larger radiation volume (≥ 250ml; HR = 0.81) were predictors of PFS. The escalated dose (HR = 0.47) and a larger radiation volume (HR = 0.76) were identified as predictors for better OS. Following detailed statistical analysis, a moderate radiation dose escalation (> 60 Gy) was found as an independent factor affecting OS in GBM patients. In conclusion, a moderate radiation dose escalation (> 60 Gy) was an independent predictor for longer OS in GBM patients. However, prospective studies including more patients with more information, such as molecular markers and completeness of resection, are needed to confirm our findings.

Clinical implications of multiple glioblastomas: An analysis of prognostic factors and survival to distinguish from their single counterparts.

PURPOSE: Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors. GBMs with synchronous multiple foci (multiple GBMs) is rarely diagnosed in the clinical scenario. This study aims to compare the clinical characteristics between multiple and single GBMs and to identify factors associated with the survival of GBM and evaluate their effects. METHODS: We retrospectively reviewed the medical records of patients with primary GBM in a referral medical center in Taiwan who were diagnosed between 2005 and 2016. They were identified from the cancer registry database of the center and followed from the date of diagnosis to october 2018. The primary endpoint of this study was overall survival (OS), and the independent factors for survival were identified through Cox regressions. RESULTS: A total of 48 patients were identified, of whom 44 GBM (92%) and 4 gliosarcoma (GSM) (8%). Preoperative images showed five (10%) patients had multiple brain lesions. GSM showed a high ratio of multiple lesions (50%) than patients with GBM (5%) (p = 0.05). Those with multiple lesions had significantly worse median OS of 8.2 months compared to patients with a single lesion (16 months, p = 0.03). We found that multiple GBMs was a predictor of worse survival (hazard ratio [HR] = 3.57, 95% confidence interval [95%CI]: 1.26-10.13) after adjusting for other significant predictor of radiotherapy (HR = 0.47, 95%CI: 0.23-0.96). CONCLUSION: Patients with multiple GBMs had worse survival compared to those with single GBM. GBM patients without post-operative radiotherapy were also a predictor of worse survival.