A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients

Background:For patients with nasopharyngeal carcinoma(NPC) who undergo re-irradiation with intensity-modulated radiotherapy(IMRT),lethal nasopharyngeal necrosis(LNN) is a severe late adverse event.The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC.Methods:Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study.Clinical characteristics,including recurrent carcinoma conditions and dosimetric features,were evaluated as candidate risk factors for LNN.Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model.Results:Among 228 patients enrolled in this study,204 were at risk of developing LNN based on risk analysis.Of the 204 patients treated,31(15.2%) developed LNN.Logistic regression analysis showed that female sex(P = 0.008),necrosis before re-irradiation(P = 0.008),accumulated total prescription dose to the gross tumor volume(GTV) ≥ 145.5 Gy(P = 0.043),and recurrent tumor volume >25.38 cm3(P = 0.009) were independent risk factors for LNN.A model to predict LNN was then constructed that included these four independent risk factors.Conclusions:A model that includes sex,necrosis before re-irradiation,accumulated total prescription dose to GTV,and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Re-irradiation for high-grade gliomas:Has anything changed?

Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams.Improved radiation therapy techniques,new imaging methods,published experience,and a better radiobiological knowledge of brain tissue have positioned re-irradiation(re-RT)as an option for many of these patients.Decisions must be individualized,taking into account the pattern of relapse,previous treatment,and functional status,as well as the patient’s preferences and expected quality of life.Many questions remain unanswered with respect to re-RT:Who is the most appropriate candidate,which dose and fractionation are most effective,how to define the target volume,which imaging technique is best for planning,and what is the optimal timing?This review will focus on describing the most relevant studies that include re-RT as salvage therapy,with the aim of simplifying decision-making and designing the best available therapeutic strategy.

Intensity Modulated Proton Therapy for Re-Irradiation of Bulky Loco-Regional Recurrent Breast Cancer: A Case Report

Patients with recurrent breast cancer to chest wall, who had previous irradiation, are difficult to manage and have limited options. Several reports described the use of photon therapy, hyperthermia, and brachytherapy. This is a case report of a 72-year-old female with Stage IIIA (pT3N1M0) invasive ductal carcinoma of the right breast status post modified radical mastectomy. The patient developed recurrence to the chest wall and one internal mammary lymph node one year later. She received 3-D conformal photon radiation therapy for this recurrence. Two years later, she had progression of the recurrence at the right chest wall and axillary and internal mammary lymph nodes. She was treated with intensity modulated proton therapy (IMPT) for a total of 6600 cGy in 33 fractions. However, four months later, she was found to have biopsy-proven isolated metastatic disease at her right bicep, which was again treated with IMPT for a dose of 6000 cGy in 20 fractions. Proton beam therapy was used in this case to spare dose to the brachial plexus, heart and lung while optimally irradiating the recurrent tumors. At last follow up, the patient is alive and has been disease free for 39 months. This report describes the technique and dosimetry for this unique case, which also reviewed recent series of re-irradiation using proton beam.

3D Conformal Re-Irradiation with Temozolamide for Recurrent Glioblastoma: A Prospective Cohort Study

Introduction and objectives: Salvage treatment of recurrent Glioblastoma (GBM) is one of the most challenging tasks in neuro-oncology. There is no standard treatment for recurrent GBM as options include resection, chemotherapy, and re-irradiation either separate or in combination. Role of concomitant temozolamide with re-irradiation in recurrent disease is still debatable. Therefore, this study evaluates efficacy of concurrent and adjuvant temozolamide with re-irradiation in management of recurrent GBM. Patients and methods: Twenty two patients with recurrent glioblastoma were eligible. Patients were treated with 3 D conformal radiotherapy. The dose ranged from 30 to 40 Gy in 1.6 to 1.8 Gy per fraction for 5 days per week. Temozolamide was administrated at 50 mg/m2 daily dose during radiation therapy. Adjuvant Temozolomide (200 mg/m2) was given orally for five days every four weeks for 4 - 6 cycles for patients who did not receive temozolamide before, and 150 mg/m2 for pretreated patients. Results: 22 patients received re-irradiation with median dose 38 Gy (range 33 - 40 Gy), concurrent with temozolamide. The time interval between primary and re-irradiation ranged from 6 to 23 months with median 12 months. The re-irradiated volume, median was 101.95 cm3 (range 30 - 375 cm3). The median cumulative maximum dose to optic system and brain stem were 53.5 Gy (range 42 - 63 Gy), and 60 Gy (range 54 - 73 Gy), respectively. Response rate was 72.7%, one patient showed complete response (4.5%), partial response and stable disease registered in 22.7% and 45.5%, respectively. The median overall survival (OS) was 10 months (range 4 - 13 months), and median progression-free (PFS) survival was 7.5 months (range 2 - 11 months). The 6 and 12 months OS rate was 100% and 56.6% respectively, and the 6 months PFS rate was 93.3%. No major acute toxicity was observed. About 70% of patients experienced grade 2 toxicity in the form of headache, nausea & vomiting, skin erythema and alopecia. The late toxicity was minimal as GI & II. Symptoms of radiation necrosis were not recorded in any patient. Conclusion: 3D conformal re-irradiation concomitant with temozolamide and adjuvant temozolamide appears effective treatment in recurrent glioblastoma. The treatment protocol is safe, feasible treatment with limited rate of toxicity and improve survival outcome.

Relief Effect of Bevacizumab on Severe Edema Induced by Re-irradiation in Brain Tumor Patients

INTRODUCTION Brain edema is a serious clinical event and could cause various neurological symptoms such as dizziness and headache.Drugs frequently used to relieve brain edema include steroid,dehydrant （e.g.,mannitol）,and diuretics.But the effects of these drugs were limited in patients with severe edema.Bevacizumab has been applied in the treatment of cerebral radiation necrosis. Case studies have reported on the application of bevacizumab in the treatment of severe brain edema. In the present study,we describe significant effects of bevacizumab on severe brain edema in patients with re-irradiation.

PhaseⅠ/Ⅱtrial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma

Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.

Salvage SBRT for Previously Irradiated Lung Cancer

Purpose: Patients with locally recurrent lung cancer after definitive radiation therapy pose a challenge in management. Surgery is often not an option and chemotherapy offers poor long-term local control. Stereotactic body radiotherapy (SBRT) was investigated in an attempt to salvage locally recurrent lung cancer. Materials and Methods: From March, 2009 to January, 2010, 8 patients who had previous definitive radiation therapy for lung cancer at least six months prior to the diagnosis of locally recurrent disease underwent SBRT. Local recurrence was documented by CT, PET, and/or biopsy. Patients had to have Karnofsky Performance Score (KPS) > 70, no distant metastases by CT/PET and brain MRI, and lesions amenable to SBRT. SBRT dose deliveries were 12 Gy x 4, 10 Gy x 5, 8 Gy x 5, or 20 Gy x 3 at the treating physician’s discretion. No adjuvant chemotherapy was delivered. Results: Eight patients were included in this study. Patient characteristics were: 6 females and 2 males;ages 50 - 85 (median 71);KPS 70 - 100 (median 80);previous stage I (T1/2 N0) in 4 and stage II/III (T1/2 N1/N2) in 3, 1 pt had limited stage small cell;previous radiation doses 50 - 68 Gy in 1.8/2.5 Gy fractions;time interval from previous RT to SBRT 8 - 57 months (median 36 months);target lesion diameters 1.2 - 7.3 cm (median 4.5 cm). With a median FU of 18 months (11 - 20 months), 7 patients are alive. Crude local/regional control to date is 86% with distant metastases in 1/7 surviving patients. Acute pulmonary toxicities: cough grade 0 7/8, grade 1 1/8;pain grade 0 6/8, grade 1 2/8;dyspnea grade 2 8/8. 1 patient died 12 months after SBRT due to complications from a hip fracture. Her disease was locally controlled at the time of death. Discussion: In carefully selected patients who recur locally after previous conventional radiation therapy for lung cancer, SBRT can offer a well tolerated salvage therapy. Further follow up is needed to assess long-term local control, survival and toxicities.