Emerging Roles of Circulating Tumor DNA for Increased Precision and Personalization in Radiation Oncology.

Recent breakthroughs in circulating tumor DNA (ctDNA) technologies present a compelling opportunity to combine this emerging liquid biopsy approach with the field of radiogenomics, the study of how tumor genomics correlate with radiotherapy response and radiotoxicity. Canonically, ctDNA levels reflect metastatic tumor burden, although newer ultrasensitive technologies can be used after curative-intent radiotherapy of localized disease to assess ctDNA for minimal residual disease (MRD) detection or for post-treatment surveillance. Furthermore, several studies have demonstrated the potential utility of ctDNA analysis across various cancer types managed with radiotherapy or chemoradiotherapy, including sarcoma and cancers of the head and neck, lung, colon, rectum, bladder, and prostate . Additionally, because peripheral blood mononuclear cells are routinely collected alongside ctDNA to filter out mutations associated with clonal hematopoiesis, these cells are also available for single nucleotide polymorphism analysis and could potentially be used to detect patients at high risk for radiotoxicity. Lastly, future ctDNA assays will be utilized to better assess locoregional MRD in order to more precisely guide adjuvant radiotherapy after surgery in cases of localized disease, and guide ablative radiotherapy in cases of oligometastatic disease.

Frameless Hypofractionated Gamma Knife Radiosurgery for Residual or Recurrent Craniopharyngioma.

BACKGROUND: The management of craniopharyngiomas is challenging, usually requiring multidisciplinary care. Gamma Knife radiosurgery (GKRS) is an essential technique for residual/recurrent craniopharyngiomas. OBJECTIVE: To evaluate the efficacy of frameless hypofractionated GKRS (hfGKRS) for craniopharyngioma and factors which affect tumor control and complications. METHODS: This retrospective study involved 24 patients managed with hfGKRS. Clinical and radiological data, tumor characteristics, and procedural details were analyzed. RESULTS: There were 15 (62.5%) female patients. The median age was 38.5 years (range, 3-66 years). The mean tumor volume was 2.4 (1.93) cm 3 , with a mean solid volume of 1.6 (1.75) cm 3 . The median marginal dose was 20 Gy (range, 18-25 Gy) delivered in a median of 5 fractions (range, 3-5). During a median radiological follow-up of 23.5 months (range, 12-50 months), tumor progression was noted in 5 (20.8%) patients. The 2-year and 4-year progression-free survival were 81.8% and 61.4%, respectively. No deaths were identified at a median clinical follow-up of 31.3 months (range, 12-54 months). Visual deficits attributable to progression were noted in 3 (12.5%) patients with pre-GKRS visual field defects. An additional 4 (16.7%) patients with pre-GKRS visual deficit developed new minor visual field defects. Four (16.7%) patients showed improvement of vision after GKRS. There were no new-onset post-GKRS hormonal deficits. CONCLUSION: The management of craniopharyngioma requires a multidisciplinary approach, and irradiation represents effective treatment option for residual/recurrent tumors after surgery. To the best of our knowledge, this is the first study that addresses the efficacy of frameless hfGKRS in managing craniopharyngiomas over sufficient follow-up.

Adult Intramedullary Pilocytic Astrocytomas: Clinical Features, Management, and Outcomes.

Purpose: Adult intramedullary pilocytic astrocytomas (PAs) are exceedingly rare. The aim of this study was to summarize our experiences in treating adult intramedullary PAs. Materials and Methods: We retrospectively reviewed the records of seven adult patients who underwent microsurgery for intramedullary PAs between 2010 and 2017. Magnetic resonance imaging was the standard radiological investigation. The diagnosis of PAs was based on pathology. All the follow-up data were obtained during office visits. Results: There were three males and four females with the mean age of 40.9 years. The tumors generally exhibited hypointensity on T1-weighted images (WI) and hyperintensity on T2WI. Contrast-enhanced T1WI showed heterogeneous enhancement. Gross total resection (GTR) of the tumor was achieved in four cases and subtotal resection (STR) was achieved in three cases. Two cases of STR received postoperative radiotherapy. One STR case had mildly residual tumor regrowth. At the last follow-up, neurological status was improved in six patients. Conclusion: The accurate diagnosis of adult intramedullary PAs depends on pathology. GTR is the best treatment and the outcome is favorable. STR increases the risk of tumor recurrence, and regular follow-up is necessary. Due to uncertain therapeutic efficacy, radiotherapy should be considered carefully for cases of STR.

Successful salvage surgery of the residual tumor after boron neutron capture therapy (BNCT): A case report.

Salvage surgery after radiation therapy is known to be associated with a high incidence of postoperative complications. We describe a case of a successful salvage surgery after BNCT. In our patient with head and neck carcinoma, cervical lymph node recurrence with adhesion to a large vessel occurred after conventional radiotherapy. This lesion responded well to BNCT. Salvage surgery was subsequently performed to remove the residual tumor. Histopathologically, the isolated tissue contained tumor cells in its center and the surrounding tissue showed severe fibrosis. However, the tissue outside of the irradiation area had almost no fibrosis. BNCT may facilitate salvage surgery after radiotherapy because it causes less injury to the surrounding tissue than conventional radiotherapy. Our experience suggests that BNCT may be a feasible preoperative treatment in patients with inoperable lesions or in those who strongly desire preservation of function.

The Role of Delayed Radiotherapy Initiation in Patients with Newly Diagnosed Glioblastoma with Residual Tumor Mass.

OBJECTIVE: Treatment for newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) includes maximum safe resection, followed by adjuvant radio(chemo)therapy (RCx) with temozolomide. There is evidence that it is safe for GBM patients to prolong time to irradiation over 4 weeks after surgery. This study aimed at evaluating whether this applies to GBM patients with different levels of residual tumor volume (RV). METHODS: Medical records of all patients with newly diagnosed GBM at our department between 2014 and 2018 were reviewed. Patients who received adjuvant radio (chemo) therapy, aged older than 18 years, and with adequate perioperative imaging were included. Initial and residual tumor volumes were determined. Time to irradiation was dichotomized into two groups (≤28 and >28 days). Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression. RESULTS: One hundred and twelve patients were included. Adjuvant treatment regimen, extent of resection, residual tumor volume, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation were statistically significant factors for overall survival (OS). Time to irradiation had no impact on progression-free survival (p = 0.946) or OS (p = 0.757). When stratified for different thresholds of residual tumor volume, survival predication via Cox regression favored time to irradiation below 28 days for patients with residual tumor volume above 2 mL, but statistical significance was not reached. CONCLUSION: Time to irradiation had no significant influence on OS of the entire cohort. Nevertheless, a statistically nonsignificant survival prolongation could be observed in patients with residual tumor volume > 2 mL when admitted to radiotherapy within 28 days after surgery.

Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development.

Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas. In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas. Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas. MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth. Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy. These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules. Trial registration: www.chictr.org.cn , identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931 .

Salvage Radiation Treatment for Primary Refractory Diffuse Large B-cell Lymphoma After Chimeric Antigen Receptor (CAR) T-cell Therapy: A Case Report.

BACKGROUND: Treatment of refractory/relapsing diffuse large B cell (R/R DLBCL) lymphoma remains a challenge. Radiation therapy (RT) has versatile roles in R/R DLBCL treatment: it can be used in the peri-transplant setting for transplant-eligible candidates, or as a salvage or palliation therapy depending on the extent of the disease in transplant-ineligible patients. The introduction of chimeric antigen receptor (CAR) T-cell therapy has changed the landscape of R/R DLBCL. RT has been used as a bridging therapy to CAR T-cell therapy in order to control disease progression during its manufacturing period. However, optimal RT and CAR T-cell therapy integration is still unknown. Salvage strategies for R/R DLBCL post-CAR T-cell therapy have been little studied. CASE REPORT: Here, we present a case of primary refractory DLBCL with residual disease post-CAR T-cell therapy successfully treated with salvage RT. CONCLUSION: Radiotherapy could be an effective salvage strategy for R/R DLBCL post-CAR T-cell therapy. Exact mechanisms await exploring.

Significance of boost dose for T4 nasopharyngeal carcinoma with residual primary lesion after intensity-modulated radiotherapy.

BACKGROUND: Previous studies showed poorer survival in T4 disease with residual lesion. To evaluate the efficacy and toxicity of a boost dose for T4 nasopharyngeal carcinoma (NPC), patients with a residual primary lesion after intensity-modulated radiotherapy (IMRT). METHODS: 398 T4 NPC patients with residual primary lesions after radical IMRT were retrospectively reviewed. An IMRT boost dose of 4-6.75 Gy was delivered to the residual lesions in 2-3 fractions. Propensity score matching (PSM) was applied to balance potential confounders between groups (ratio, 1:2). The presence of Epstein-Barr virus (EBV) DNA in plasma after IMRT was used for risk stratification. RESULTS: Patients who received boost radiation had significantly improved overall survival (OS) and local recurrence-free survival (LRFS) compared with those who did not (all P < 0.05). In the matched cohort, 3-year OS was 86.6% in the boost radiation group and 72.7% in the non-boost group (P = 0.022). Three-year LRFS was 93.4% in the boost radiation group and 83.5% in the non-boost group (P = 0.022). In the subgroup analysis, boost dose was shown to significantly improve 3-year OS (88.0% vs. 74.1%, P = 0.021) in the low-risk group (with undetectable plasma EBV DNA after IMRT). The administration of a boost dose also improved 3-year OS in the high-risk group (with detectable plasma EBV DNA after IMRT) (66.7% vs. 60.0%, P = 0.375). Multivariate analysis demonstrated that boost dose was the only protective prognostic factor. CONCLUSION: The addition of a boost dose for T4 NPC patients with residual primary lesion after radical IMRT provides satisfactory tumor control and clinical benefit. Additional timely and effective strengthening treatments are recommended for patients with detectable levels of plasma EBV DNA after radiotherapy.

Iodine-125 Brachytherapy Can Prolong Progression-Free Survival of Patients with Locoregional Recurrence and/or Residual Hepatocellular Carcinoma After Radiofrequency Ablation.

Background: Radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) is limited by locoregional recurrence and/or residual tumors caused by incomplete ablation. Iodine-125 (125I) brachytherapy can achieve a high local control rate in solid carcinoma, but few studies have assessed the efficacy of this treatment for locoregional recurrence and/or residual HCC after RFA. Objective: To investigate the effectiveness and safety of 125I brachytherapy for treating locoregional recurrence and/or residual HCC in patients treated with RFA. Methods: Eligible study patients were those with locoregional recurrence and/or residual HCC on abdominal imaging performed 1 month after RFA at this institution between February 2009 and September 2014 retrospectively. Patients were divided into either the control group (no treatment until the tumor progressed) or the treatment group (underwent 125I brachytherapy). Progression-free survival (PFS), overall survival (OS), and complications of 125I brachytherapy were evaluated. Results: A total of 42 patients were included in the final analysis, including 29 in the control group and 13 in the treatment group. A total of 457 125I particles were used (mean 32.8 ± 21.3 mCi per case). The median follow-up time was 25 months. Median PFS was 9 months in the control group and 18 months in the treatment group (p = 0.026). The median OS was 28 months in the control group and 33 months in the treatment group (p = 0.441). There were no major complications observed in patients treated with 125I brachytherapy. Conclusion: Iodine-125 brachytherapy can prolong PFS in patients with locoregional recurrence and/or residual HCC after RFA.

Combination of Olaparib and Radiation Therapy for Triple Negative Breast Cancer: Preliminary Results of the RADIOPARP Phase 1 Trial.

PURPOSE: Preclinical studies have evidenced that triple-negative breast cancer (TNBC) cell lines are more sensitive to poly (ADP-ribose) polymerase inhibitors. This provides a strong rationale for developing a new therapeutic approach for TNBC management based on poly (ADP-ribose) polymerase inhibition. The primary goal of the RADIOPARP phase 1 trial was to evaluate the dose-limiting toxicities (DLT) and the maximum tolerated dose of olaparib combined with locoregional radiation therapy. METHODS AND MATERIALS: RADIOPARP was a single institutional phase 1 trial which evaluated olaparib-radiation therapy combination in patients with inflammatory, locoregionally advanced or metastatic TNBC who received neoadjuvant chemotherapy. Radiation therapy delivered 50 Gy to the breast or to the chest wall. Lymph nodes could be included in target volumes according to local guidelines. The dose-finding toxicity-based study was conducted in sequential and adaptive Bayesian scheme using the time-to-event continual reassessment method, with 4 olaparib dose levels (50 mg, 100 mg, 150 mg, and 200 mg twice per day). RESULTS: Twenty-four patients with Eastern Cooperative Oncology Group Performance Status of 0 or 1 were enrolled from September 2017 to November 2019. Twenty-one patients (87.5%) received the olaparib-radiation therapy combination after breast surgery owing to residual disease after neoadjuvant chemotherapy, and the 3 other patients (12.5%) had unresectable tumors which were refractory to neoadjuvant chemotherapy. All patients received full course combination treatment as follows: 4 patients (pts) at 50 mg twice a day, 8 pts at 100 mg twice a day, 7 pts at 150 mg twice a day, and 5 pts at 200 mg twice a day. No DLT was observed. CONCLUSIONS: Olaparib was escalated to the maximum target dose of 200 mg twice a day without DLT. Further follow-up is needed to evaluate the late toxicities. Pending the long-term results of the RADIOPARP trial, we suggest using 200 mg of olaparib twice per day for future trials.

Salvage chemoradiation therapy for recurrence after radical surgery or palliative surgery in esophageal cancer patients: a prospective, multicenter clinical trial protocol.

BACKGROUND: Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell cancer (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety. METHODS: Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established. DISCUSSION: This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection. TRIAL REGISTRATION: Prospectively Registered. ClinicalTrials.gov NCT03731442 , Registered November 6, 2018.

Residual Site Radiotherapy After Immunochemotherapy in Primary Mediastinal B-Cell Lymphoma: A Monoinstitutional Retrospective Study.

AIM: To evaluate the efficacy of residual site radiation therapy (RSRT) on local control (LC), progression-free (PFS) and overall (OS) survival in patients with primary mediastinal lymphoma (PMBCL), following rituximab and chemotherapy treatment (ICHT). PATIENTS AND METHODS: The study included 34 patients with PMBCL treated between 2006 and 2014 with ICHT with/without autologous stem cell transplantation and RSRT. Between the end of ICHT/stem cell transplantation and RSRT, patients were evaluated with 18F-fluorodeoxyglucose positron-emission tomography. The gross tumor volume included morphological mediastinal residual disease after ICHT/SCT. The percentage of LC, PFS and OS were assessed. RESULTS: All patients received RSRT with a median dose of 30 Gy. Median follow-up was 82 months. One patient out of 34 (3%) showed progressive disease 9 months from diagnosis. The 10-year PFS and OS were 97% and 97% respectively. CONCLUSION: RSRT in patients with PMBCL treated with ICHT did not impact unfavorably on LC and patient survival.

Efficacy of radiation boost after breast-conserving surgery for breast cancer with focally positive, tumor-exposed margins.

Many patients with positive margins following breast-conserving surgery (BCS) undergo re-excisions that aim to remove residual disease from the breast, which brings a tremendous emotional burden in addition to financial consequences. We sought to determine whether re-excisions could be safely avoided without compromising local control and survival by using whole-breast radiation therapy (WBRT) with a tumor bed boost in patients with early-stage breast cancer with focally positive, tumor-exposed margins after BCS. All patients with ductal carcinoma in situ (DCIS) and/or invasive breast cancer (IBC) who had pathologically tumor-exposed margins following BCS, without re-excision and treated with WBRT with tumor bed boost between March 2005 and December 2011, were included. The radiotherapy consisted of WBRT at a dose of 50 Gy in 25 fractions, followed by a tumor bed boost with an additional dose of 16 Gy in eight fractions. A total of 125 patients fulfilled the eligibility criteria; of the 125 patients, 1 had bilateral breast cancer, resulting in 126 cases. Invasive disease was found in 102 (81%) cases and purely ductal carcinoma in situ (DCIS) disease in 24 (19%) cases. The 10-year ipsilateral breast tumor recurrence (IBTR) -free survival, progression-free survival (PFS), and 10-year overall survival (OS) rates were 95%, 92.5% and 96%, respectively. Patients with early-stage breast cancer who receive BCS and have focally positive, tumor-exposed margins can avoid re-excision by undergoing WBRT followed by a sufficient dose of tumor bed boost, without negatively impacting local control and survival.

Developing more sensitive genomic approaches to detect radioresponse in precision radiation oncology: From tissue DNA analysis to circulating tumor DNA.

Despite the common application and considerable efforts to achieve precision radiotherapy (RT) in several types of cancer, RT has not yet entered the era of precision medicine; the ability to predict radiosensitivity and treatment responses in tumors and normal tissues is lacking. Therefore, development of genome-based methods for individual prognosis in radiation oncology is urgently required. Traditional DNA sequencing requires tissue samples collected during invasive operations; therefore, repeated tests are nearly impossible. Intra- and inter-tumoral heterogeneity may undermine the predictive power of a single assay from tumor samples. In contrast, analysis of circulating tumor DNA (ctDNA) allows for non-invasive and near real-time sampling of tumors. By investigating the genetic composition of tumors and monitoring dynamic changes during treatment, ctDNA analysis may potentially be clinically valuable in prediction of treatment responses prior to RT, surveillance of responses during RT, and evaluation of residual disease following RT. As a biomarker for RT response, ctDNA profiling may guide personalized treatments. In this review, we will discuss approaches of tissue DNA sequencing and ctDNA detection and summarize their clinical applications in both traditional RT and in combination with immunotherapy.

Solitary Extra-axial Intracranial Primary Meningeal Pleomorphic Xanthoastrocytoma: An Extremely Rare Case.

BACKGROUND: Pleomorphic xanthoastrocytomas (PXAs) are a rare type of astrocytoma, which, similar to other gliomas, can rarely arise from glial nests in the meninges, manifesting as an extra-axial mass. We describe a solitary extra-axial intracranial primary meningeal PXA in the pediatric age group, which was masquerading as a tentorial meningioma. CASE DESCRIPTION: A 9-year-old girl presented with features of raised intracranial pressure. Imaging revealed a dural-based mass in the tentorial region suggestive of a meningioma. This suspicion was further strengthened by intraoperative visualization of an extra-axial tumor with wide tentorial attachment. Near-total excision was achieved. Histopathologic examination established the diagnosis of PXA. Given the tumor's apparent meningeal origin and lack of connection with brain parenchyma in imaging and intraoperative findings, primary meningeal PXA was diagnosed. The absence of coexisting tumor foci on spinal magnetic resonance imaging further refined the diagnosis as solitary extra-axial intracranial primary meningeal PXA. The patient received radiotherapy for the residual tumor and was doing well at 6 months after presentation; however, she was lost to follow-up after that. CONCLUSIONS: Solitary extra-axial intracranial primary meningeal PXA is an extremely rare entity with only 3 reported cases in the literature including the present case. This is the first report of such a tumor in a pediatric patient. This report also highlights that primary meningeal PXA can manifest as an extra-axial mass lesion and may warrant inclusion in the differential diagnosis of extra-axial mass lesions.

The Role of Leksell Radiosurgery in the Management of Craniopharyngiomas.

Management of craniopharyngiomas remains challenging due to the tumor's often intimate relationship with the optic apparatus, the hypothalamus, and the pituitary gland. Often multimodal management is needed to achieve the best treatment outcome: tumor control coupled with endocrine, visual, and neurocognitive preservation. Many surgeons favor initial subtotal resection followed by adjunctive therapy to improve quality of life in a tumor with potentially long-term survival even if coupled with a need for periodic new interventions. During the patient's subsequent follow-up, solid or cystic tumor recurrence or progression often require additional management options. Leksell stereotactic radiosurgery (SRS) is a valuable adjuvant strategy that enhances long-term outcomes in patients with residual or recurrent craniopharyngiomas. Tumor control rates of 70-90% have been reported using 11- to 13-Gy tumor margin doses delivered using the Gamma Knife. Smaller tumors are associated with better radiosurgery outcomes. SRS is an effective management for residual or recurrent solid craniopharyngiomas with a favorable benefit-to-risk profile.

Radiosurgery for Chordoma and Chondrosarcoma.

Chordomas and chondrosarcomas are rare locally aggressive skull base tumors with high progression or recurrence rates. Ultimately, they have high mortality rates unless they respond to multimodality management options that include one or more surgical resections, fractionated radiation therapy, and stereotactic radiosurgery (SRS). SRS has become a standard management option for recurrent or residual chordomas and chondrosarcomas after failed surgical resection and fractionated radiation therapy. This report examines the role of SRS in these skull base tumors.

Salvage Leksell Stereotactic Radiosurgery for Malignant Gliomas.

The outcome of patients with malignant gliomas has not substantially improved, even with advances in imaging, neurosurgery, molecular subtyping, and radiation, and newer oncologic options. Maximal safe resection when feasible remains the initial treatment of choice for most malignant gliomas. These tumors often recur and require additional therapy to control the tumor growth. Leksell stereotactic radiosurgery (SRS) is offered as salvage therapy in patients with recurrent or residual malignant gliomas. SRS is well tolerated and is associated with a relatively low risk of adverse radiation effects in malignant glial tumor patients who otherwise have relatively few options. SRS allows the surgeon more flexibility in terms of surgical options and may enhance quality of life for patients postoperatively. Although randomized controlled studies are lacking in the use of salvage SRS after the failure of initial standard of care management, preliminary data suggest that radiosurgery improves tumor control and overall survival for patients with recurrent malignant gliomas.

Radiosurgery for Central Neurocytoma.

The classification of central neurocytoma (CN) by the WHO was upgraded to grade 2 in 1993 as it was recognized that at least some of these tumors can exhibit more aggressive behavior. Currently, as of 2016, CN is classified as WHO grade 2. Indeed, some atypical variants have been reported and residual postsurgical tumor is believed to have the potential for malignant transformation. Although gross total resection is usually curative for CN (5-year survival rate 99%), it is achieved in nearly 30-50% of cases due to its central location. Adjuvant treatments should be deliberately considered for the optimal management of CN. Recently, stereotactic radiosurgery is increasingly proposed as an adjuvant treatment for CN.

Efficacy of proton therapy in children with high-risk and locally recurrent neuroblastoma.

PURPOSE: Proton therapy is currently used in the management of pediatric tumors to decrease late toxicities. However, one of the criticisms of proton therapy is the limited data regarding efficacy on disease control. The purpose of this study was to examine local and distant control rates after proton therapy for neuroblastoma. METHODS AND MATERIALS: Eighteen patients with high-risk (n = 16) and locally recurrent neuroblastoma (n = 2) were treated with curative intent and received proton therapy to the primary site and up to three post-induction MIBG-avid metastatic sites. Primary sites (n = 18) were treated to 21-36 Gy (relative biological effectiveness [RBE]), and metastatic sites (n = 16) were treated to 21-24 Gy (RBE). Local control and survival rates were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 60.2 months, two- and five-year local control rates at the irradiated primary site were 94% and 87%, respectively. No failures at irradiated distant metastatic sites were observed. The five-year progression-free survival (PFS) was 64%, and the five-year overall survival (OS) was 94%. The extent of surgical resection was not associated with local control, PFS, or OS. No radiation-related nephropathy or hepatopathy was reported. CONCLUSIONS: Excellent local control was achieved using proton therapy to the primary and post-induction MIBG-positive distant sites. The predominant site of failure is progression in post-induction non-MIBG-avid distant sites. Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, further advances in systemic therapy are needed for the improved control of systemic disease.