Mark W. McDonald

Pattern of Failure after Limited Margin Radiotherapy and Temozolomide for Glioblastoma

PURPOSE To evaluate the pattern of failure after limited margin radiotherapy for glioblastoma. METHODS AND MATERIALS We analyzed 62 consecutive patients with newly diagnosed glioblastoma treated between 2006 and 2008 with standard fractionation to a total dose of 60 Gy with concurrent temozolomide (97%) or arsenic trioxide (3%). The initial clinical target volume included postoperative T2 abnormality with a median margin of 0.7 cm. The boost clinical target volume included residual T1-enhancing tumor and resection cavity with a median margin of 0.5 cm. Planning target volumes added a 0.3- or 0.5-cm margin to clinical target volumes. The total boost planning target volume (PTV(boost)) margin was 1cm or less in 92% of patients. The volume of recurrent tumor (new T1 enhancement) was categorized by the percent within the 60-Gy isodose line as central (>95%), infield (81-95%), marginal (20-80%), or distant (<20%). For comparison, an initial planning target volume with a 2-cm margin and PTV(boost) with a 2.5-cm margin were created for each patient. RESULTS With a median follow-up of 12 months, radiographic tumor progression developed in 43 of 62 patients. Imaging was available for analysis in 41: 38 (93%) had central or infield failure, 2 (5%) had marginal failure, and 1 (2%) had distant failure relative to the 60-Gy isodose line. The treated PTV(boost) (median, 140 cm(3)) was, on average, 70% less than the PTV(boost) with a 2.5-cm margin (median, 477 cm(3)) (p < 0.001). CONCLUSIONS A PTV(boost) margin of 1cm or less did not appear to increase the risk of marginal and/or distant tumor failures compared with other published series. With careful radiation planning and delivery, it appears that treatment margins for glioblastoma can be reduced.

Risk of Carotid Blowout After Reirradiation of the Head and Neck: A Systematic Review

PURPOSE Carotid blowout (CB) is a rare but frequently fatal complication of head-and-neck (H&N) cancer or its treatment. We sought to determine the reported rate of CB in patients receiving salvage reirradiation for H&N cancer. METHODS AND MATERIALS A literature search identified 27 published articles on H&N reirradiation involving 1554 patients, and a pooled analysis was performed to determine the rate of CB. Treatment parameters, including prior radiation dose, interval from prior radiation, dose and fractionation of reirradiation, use of salvage surgery, and chemotherapy, were abstracted and summarized. The cumulative risk of CB was compared between groups using Fishers exact test. RESULTS Among 1554 patients receiving salvage H&N reirradiation, there were 41 reported CBs, for a rate of 2.6%; 76% were fatal. In patients treated in a continuous course with 1.8-2-Gy daily fractions or 1.2-Gy twice-daily fractions, 36% of whom received concurrent chemotherapy, the rate of CB was 1.3%, compared with 4.5% in patients treated with 1.5 Gy twice daily in alternating weeks or with delayed accelerated hyperfractionation, all of whom received concurrent chemotherapy (p = 0.002). There was no statistically significant difference in the rate of CB between patients treated with or without concurrent chemotherapy, or between patients treated with or without salvage surgery before reirradiation. CONCLUSION Carotid blowout is an infrequent but serious complication of salvage reirradiation for H&N cancer. The rate of CB was lower among patients treated with conventional or hyperfractionated schedules compared with regimens of accelerated hyperfractionation, though heterogeneous patient populations and treatment parameters preclude definite conclusions. Given the high mortality rate of CB, discussion of the risk of CB is an important component of informed consent for salvage reirradiation.

Long-term outcomes of IMRT for breast cancer: a single-institution cohort analysis.

PURPOSE To evaluate long-term outcomes of adjuvant breast intensity-modulated radiation therapy (IMRT), with a comparison cohort receiving conventional radiation (cRT) during the same period. METHODS AND MATERIALS Retrospective review identified patients with Stages 0-III breast cancer who underwent irradiation after conservative surgery from January 1999 to December 2003. Computed tomography simulation was used to design standard tangential breast fields with enhanced dynamic wedges for cRT and both enhanced dynamic wedges and dynamic multileaf collimators for IMRT. Patients received 1.8-2-Gy fractions to 44-50.4 Gy to the whole breast, followed by an electron boost of 10-20 Gy. RESULTS A total of 245 breasts were treated in 240 patients: 121 with IMRT and 124 with cRT. Median breast dose was 50 Gy, and median total dose was 60 Gy in both groups. Patient characteristics were well balanced between groups. Median follow-ups were 6.3 years (range, 3.7-104 months) for patients treated with IMRT and 7.5 years (range, 4.9-112 months) for those treated with cRT. Treatment with IMRT decreased acute skin toxicity of Radiation Therapy Oncology Group Grade 2 or 3 compared with cRT (39% vs. 52%; p = 0.047). For patients with Stages I-III (n = 199), 7-year Kaplan-Meier freedom from ipsilateral breast tumor recurrence (IBTR) rates were 95% for IMRT and 90% for cRT (p = 0.36). For patients with Stage 0 (ductal carcinoma in situ, n = 46), 7-year freedom from IBTR rates were 92% for IMRT and 81% for cRT (p = 0.29). Comparing IMRT with cRT, there were no statistically significant differences in overall survival, disease-specific survival, or freedom from IBTR, contralateral breast tumor recurrence, distant metastasis, late toxicity, or second malignancies. CONCLUSIONS Patients treated with breast IMRT had decreased acute skin toxicity, and long-term follow-up shows excellent local control similar to a contemporaneous cohort treated with cRT.

ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation expert panel on radiation oncology-head and neck cancer.

Recurrent and second primary head-and-neck squamous cell carcinomas arising within or in close proximity to previously irradiated fields are a common clinical challenge. Whereas surgical salvage therapy is recommended for resectable disease, randomized data support the role of postoperative reirradiation in high-risk patients. Definitive reirradiation is an established approach for patients with recurrent disease who are medically or technically inoperable or decline radical surgery. The American College of Radiology Expert Panel on Head and Neck Cancer reviewed the relevant literature addressing re-treatment after prior definitive radiation and developed appropriateness criteria for representative clinical scenarios. Examples of unresectable recurrent disease and microscopic residual disease after salvage surgery were addressed. The panel evaluated the appropriateness of reirradiation, the integration of concurrent chemotherapy, radiation technique, treatment volume, dose, and fractionation. The panel emphasized the importance of patient selection and recommended evaluation and treatment at tertiary-care centers with a head-and-neck oncology team equipped with the resources and experience to manage the complexities and toxicities of re-treatment.

Three-Year Outcomes of Breast Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost

PURPOSE To report our clinical experience using breast intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT). METHODS AND MATERIALS Retrospective review identified 354 Stage 0 to III breast cancer patients treated with SIB-IMRT after conservative surgery between 2003 and 2006. The most common fractionation (89%) simultaneously delivered 1.8 Gy to the ipsilateral breast tissue and 2.14 Gy to the resection cavity, yielding a breast dose of 45 Gy (25 fractions) and cavity dose 59.92 Gy (28 fractions), biologically equivalent for tumor control to 45 Gy to the breast with sequential 16-Gy boost (33 fractions). RESULTS A total of 356 breasts in 354 patients were treated: 282 with invasive breast cancer, and 74 with ductal carcinoma in situ (DCIS). For left breast radiation, median cardiac V(15) was 2.9% and left ventricular V(15) 1.7%. Median follow-up was 33 months (range, 4-73 months). Acute toxicity was Grade 1 in 57% of cases, Grade 2 in 43%, and Grade 3 in <1%. For invasive breast cancer, the 3-year overall survival was 97.6% and risk of any locoregional recurrence was 2.8%. For ductal carcinoma in situ, 3-year overall survival was 98% and risk of locoregional recurrence 1.4%. In 142 cases at a minimum of 3 years follow-up, global breast cosmesis was judged by physicians as good or excellent in 96.5% and fair in 3.5%. CONCLUSIONS Breast SIB-IMRT reduced treatment duration by five fractions with a favorable acute toxicity profile and low cardiac dose for left breast treatment. At 3 years, locoregional control was excellent, and initial assessment suggested good or excellent cosmesis in a high percentage of evaluable patients.

Infant brain tumors: Incidence, survival, and the role of radiation based on surveillance, epidemiology, and end results (SEER) data

PURPOSE To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. METHODS AND MATERIALS The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. RESULTS Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). CONCLUSION The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone.

Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

PURPOSE To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. METHODS AND MATERIALS A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy). Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm(3) (range, 0-701 cm(3)). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). RESULTS The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. CONCLUSIONS Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional toxicities may develop with longer follow-up times.

American College of Radiology appropriateness criteria on multiple brain metastases.

EXPERT PANEL ON RADIATION ONCOLOGY–BRAIN METASTASES; GREGORY M. M. VIDETIC, M.D.,* LAURIE E. GASPAR, M.D., M.B.A.,y AMR M. AREF, M.D.,z ISABELLE M. GERMANO, M.D.,x BRIAN J. GOLDSMITH, M.D.,k JOSEPH P. IMPERATO, M.D.,{ KAREN J. MARCUS, M.D., MICHAEL W. MCDERMOTT, M.D.,** MARK W. MCDONALD, M.D.,yy ROY A. PATCHELL, M.D.,zz H. IAN ROBINS, M.D., PH.D.,xx C. LELAND ROGERS, M.D.,kk JOHN H. SUH, M.D.,* AARON H. WOLFSON, M.D.,{{ AND FRANZ J. WIPPOLD, II, M.D.

ACR Appropriateness Criteria®: Single Brain Metastasis

Single brain metastasis represents a common neurologic complication of cancer. Given the number of treatment options that are available for patients with brain metastasis and the strong opinions that are associated with each option, appropriate treatment for these patients has become controversial. Prognostic factors such as recursive partitioning analysis and graded prognostic assessment can help guide treatment decisions. Surgery, whole brain radiation therapy (WBRT), stereotactic radiosurgery or combination of these treatments can be considered based on a number of factors. Despite Class I evidence suggestive of best therapy, the treatment recommendation is quite varied among physicians as demonstrated by the American College of Radiologys Appropriateness Panel on single brain metastasis. Given the potential concerns of the neurocognitive effects of WBRT, the use of SRS alone or SRS to a resection cavity has gained support. Since aggressive local therapy is beneficial for survival, local control and quality of life, the use of these various treatment modalities needs to be carefully investigated given the growing number of long-term survivors. Enrollment of patients onto clinical trials is important to advance our understanding of brain metastasis.

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck

Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3-4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100 mg/m(2) every 21 days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63 Gy for high-risk patients and at least 57 Gy for low risk patients.