The evolving role of reirradiation in the management of recurrent brain tumors.

Despite aggressive management consisting of surgery, radiation therapy (RT), and systemic therapy given alone or in combination, a significant proportion of patients with brain tumors will experience tumor recurrence. For these patients, no standard of care exists and management of either primary or metastatic recurrent tumors remains challenging.Advances in imaging and RT technology have enabled more precise tumor localization and dose delivery, leading to a reduction in the volume of health brain tissue exposed to high radiation doses. Radiation techniques have evolved from three-dimensional (3-D) conformal RT to the development of sophisticated techniques, including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and stereotactic techniques, either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Several studies have suggested that a second course of RT is a feasible treatment option in patients with a recurrent tumor; however, survival benefit and treatment related toxicity of reirradiation, given alone or in combination with other focal or systemic therapies, remain a controversial issue.We provide a critical overview of the current clinical status and technical challenges of reirradiation in patients with both recurrent primary brain tumors, such as gliomas, ependymomas, medulloblastomas, and meningiomas, and brain metastases. Relevant clinical questions such as the appropriate radiation technique and patient selection, the optimal radiation dose and fractionation, tolerance of the brain to a second course of RT, and the risk of adverse radiation effects have been critically discussed.

Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma.

PURPOSE: To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation. METHODS: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4-54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis. RESULTS: With a median follow-up time of 9.0 years (range, 1.3-15 years), median PFS and OS times were 9 years (95%CI, 6.6-10.3) and 11.8 years (95%CI, 9.3-13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16-0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33-1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08-0.87; p = 0.01). CONCLUSIONS: TMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.

Clinical Efficacy of Adjuvant Radiotherapy for World Health Organization Grade II Intracranial Meningioma.

BACKGROUND: Maximal surgical resection remains the treatment of choice for grade II meningiomas, and for some authors it is sufficient to guarantee a long indolent course even without postsurgical radiotherapy (RT), but there is no consensus on the use of RT in this patient population. METHODS: We retrospectively compared clinical and radiologic outcomes between World Health Organization grade I (group A) and grade II (group B) surgically treated meningiomas, focusing on the role of adjuvant RT. We registered clinical, surgical, and radiologic data to detect differences in survival and functional outcome between the 2 groups. RESULTS: The final cohort consisted of 284 patients for group A and 94 patients for group B. Group B showed a higher risk of developing recurrence independently of the extent of resection (7.75% for Group A vs. 27.7% for Group B, P = 0.01). Patients who did not undergo adjuvant RT documented recurrence in 50% of cases, compared with 19% of patients who underwent RT (P = 0.024). There is a weak difference in the risk of developing postoperative seizures in the group submitted to radiotherapy (P = 0.08). Performance status remained stable for both groups, but for Group B it tended to decrease significantly after 1 year with regard to extent of resection and RT. CONCLUSIONS: Recurrence is more frequent for grade II meningiomas, even though there are no significant differences in terms of complications and functional outcome. Radiotherapy in grade II meningiomas does indeed lead to better control of recurrence but leads to an increased risk of seizures and reduced performance status.

Relationship between Salivary Amylase and Xerostomia in Intensity-Modulated Radiation Therapy for Head and Neck Cancer: A Prospective Pilot Study.

PURPOSE: A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices. RESULTS: Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = -0.70) and late (ρ = -0.80) xerostomia. CONCLUSION: Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.

The INCH Trial - Induction Chemotherapy in Patients With Bulky Anal Canal Cancer: Evaluation of the Pilot Phase.

AIM: To assess feasibility, complications and efficacy of induction chemotherapy followed by standard chemoradiotherapy in patients with bulky anal canal cancer. PATIENTS AND METHODS: Patients with squamous cell carcinoma of the anal canal, staged bulky tumor with or without nodal involvement were prospectively enrolled. Before standard chemoradiotherapy, patients received induction chemotherapy with 3 cycles of 75 mg/m2 cisplatin and 750 mg/m2 5-fluorouracil. Patients were followed-up routinely until recurrence or death. RESULTS: Seven patients with bulky anal canal cancer were evaluable for this pilot phase of the study. All patients had human papillomavirus-negative disease. Five completed the scheduled induction chemotherapy and all patients completed the programmed concomitant chemoradiotherapy. None had severe hematological toxicity. The majority of patients (6/7) had tumor downsizing after induction treatment. Six months after chemoradiotherapy, complete response was documented in three patients and salvage surgery was performed in two cases. With a median follow-up of 38 months (range=28-48 months), two patients are disease-free survivors. CONCLUSION: Induction chemotherapy has the potential to become a standard approach in patients with bulky human papillomavirus-negative anal canal cancer.