The impact of adjuvant therapy for patients with high-risk diffuse WHO grade II glioma.

Despite recent randomized, prospective evidence supporting use of RT and chemotherapy (CRT) for high-risk low-grade gliomas (LGG), many patients have historically received RT alone, chemotherapy alone or observation postoperatively. The purpose of this study is to evaluate outcomes for historical treatments in comparison to CRT for high-risk diffuse WHO grade II glioma patients. Records from 309 adults with WHO grade II glioma (1997-2008) eligible for RTOG 9802 (incomplete resection/biopsy or age ≥40 years) were retrospectively reviewed. Kaplan-Meier estimates were used for progression-free survival (PFS) and overall survival (OS). The Cox proportional hazards model was used for estimates of risk ratios for univariate and multivariate analyses. Median follow-up was 10.6 years. Adjuvant treatments included radiotherapy (RT) alone (45%), observation (31%), CRT (21%) and chemotherapy alone (3%). Non-astrocytic histology, TERT promoter mutation, 1p/19q codeletion and extensive resections were associated with improved PFS and OS on univariate analysis (all p < 0.05). IDH mutations and adjuvant CRT was associated with improved PFS (all p < 0.05). On multivariate analysis, histology, molecular grouping and extent of resection were significantly associated with PFS and OS. In addition, multivariate analysis revealed that CRT was associated with improved PFS and OS compared with RT alone, and improved PFS compared with observation. This study confirms the benefit of adding chemotherapy to RT compared with RT alone or observation. These findings emphasize the need for aggressive treatment in patients with high-risk LGG.

Patterns of care and treatment outcomes in older adults with low grade glioma: a 50-year experience.

The purpose of this study was to identify changes in presentation, treatment and outcomes of older patients with low-grade glioma (LGG) over the past 50 years. 94 adults aged 55 or older upon diagnosis of a WHO grade II LGG at Mayo Clinic between 1960 and 2011 were included and grouped by those diagnosed before (group I: 1960-1989) and after (group II: 1990-2011) the routine use of post-operative MRI. Median follow-up was 11.4 years. Pathologic diagnoses included astrocytoma in 55%, mixed oligoastrocytoma in 18% and oligodendroglioma in 27%. Gross total resection (GTR) was achieved in 10%, radical subtotal resection (rSTR) in 6%, subtotal resection (STR) in 20% and biopsy only in 64%. Post-operative radiotherapy (PORT) was given in 77%. More patients in the modern era received GTR/rSTR (20 vs. 7%), though the difference was not statistically significant. Median progression-free survival (PFS) was 3.0 years, with 5- and 10-year PFS rates of 31 and 10%, respectively. Median, 5- and 10-year overall survival (OS) was 4.1 years, 43 and 17%, respectively. PFS and OS did not improve in the modern era. Factors negatively associated with PFS on multivariate analysis included astrocytoma histology, contrast enhancement and STR/biopsy. Factors associated with poor OS on multivariate analysis included astrocytoma histology, deep location, contrast enhancement and STR/biopsy. Despite reports of improving outcomes for younger patients treated in the modern era, outcomes have not significantly improved for older patients. Further efforts to improve outcomes based on molecular genotyping are needed to determine a rational strategy for treatment intensification.

Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis.

BACKGROUND: The local-regional management of female breast cancer has been extensively investigated worldwide. The optimal approach for males diagnosed with breast cancer is less clear. We have analyzed the treatment of male breast cancer using a population-based national registry to determine the impact of surgery and radiation therapy on survival. MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried to identify males with invasive ductal carcinoma of the breast who underwent primary surgical resection (radical mastectomy, modified radical mastectomy, total mastectomy, or segmental) for the years 1983 to 2002. Demographic, clinical, and pathologic data were culled and analyzed to determine the impact of radiation therapy (RT) following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (P<0.05). Multivariate analysis with the Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS). RESULTS: A total of 1337 patients met the eligibility criteria and were analyzed. Median follow-up was 7.3 years (range, 1 mo to 25 y). Most men underwent modified radical mastectomy (n=1062) with a minority undergoing segmental (n=113). About 329 men received postoperative external beam RT. The median rates of OS and CSS for all men were 10.5 years and not yet reached, respectively. The surgical procedure did not significantly associate with OS or CSS. By stage, RT was associated with improved OS for stage I (P=0.03). There was a trend for improved survival with stage II (P=0.21) and III (P=0.15). RT was not associated with improved CSS by stage. RT improved rates of OS and CSS in N2 patients without reaching statistical significance (P=0.10 and 0.22). On multivariate analysis, advancing age, stage and grade, and no postoperative RT predicted for worse OS. However, when controlled for those with known hormone receptor status (n=978), only the factors of advancing age, stage, grade, and hormone receptor negativity predicted for worse OS. Advancing age, stage, and grade were the only predictors of CSS irrespective of the cohort analyzed. CONCLUSIONS: The primary surgical procedure did not ultimately influence OS or CSS in this population-based registry of males with breast cancer. A statistically nonsignificant improvement with postoperative RT was observed in men with lymph node involvement, larger tumor size, or higher stage. When controlled for age, stage, and grade in multivariate analysis, postoperative RT predicted for improved OS but not CSS. These data suggest a beneficial effect of RT in the postoperative setting. A prospective study is necessary to further elucidate appropriate treatment strategies for men with breast cancer.

Long-term Treatment Outcomes for Locally Advanced Esophageal Cancer: A Single-Institution Experience.

OBJECTIVES: To determine long-term outcomes in patients with locally advanced esophageal carcinoma treated with trimodality therapy (chemoradiotherapy [CRT] and surgery, TMT) or definitive CRT. METHODS: We retrospectively identified patients with advanced esophageal carcinoma treated with curative intent at our institution between 1998 and 2004. Identified patients were separated into 3 groups: patients who received TMT, patients who received CRT, and patients who began treatment with trimodality intent but did not undergo surgery (PTMT). Local control, overall survival (OS), and distant metastasis-free survival were compared using Kaplan-Meier statistics. RESULTS: Among the 265 patients included, median follow-up was 6.4 years for surviving patients and 1.7 years for all patients. Type of esophageal cancer was adenocarcinoma in 213 patients (80%) and squamous cell carcinoma in 46 patients (17%). Treatment groups comprised 169 patients (64%) completing TMT, 46 patients medically unable to undergo surgery after neoadjuvant therapy (PTMT), and 50 (19%) who underwent CRT. Median OS was 20.5 months; actuarial 5- and 10-year OS were 27% and 12%, respectively. The TMT group had the highest 5- and 10-year OS (32% and 19%, respectively). Local control rates at 2, 5, and 10 years for all patients were 80%, 70%, and 69%, respectively. By treatment modality, 5-year local control was best (82%) for TMT, compared with 60% for CRT and 40% for PTMT groups (P<0.001). CONCLUSIONS: Patients who completed TMT had the best local control and long-term OS. In the context of TMT, surgery seemed more beneficial in patients with esophageal adenocarcinoma versus squamous cell carcinoma.

Breast conservation therapy utilizing partial breast brachytherapy for early-stage cancer of the breast: a retrospective review from the Saint Luke's Cancer Institute.

BACKGROUND: Accelerated partial breast irradiation (APBI) is a convenient alternative to whole-breast irradiation, as less overall time is needed for completion. The use of APBI outside the framework of large prospective clinical trials has markedly increased. To our knowledge, no high-volume, community-based breast program has published their experience with APBI. METHODS: The records of 93 consecutive patients who underwent APBI utilizing Mammosite Radiation Therapy System from 2005 to 2010 at Saint Luke's Cancer Institute in Kansas City, MO, were retrospectively reviewed. The Kaplan-Meier method was used to estimate the ipsilateral breast recurrence rate and recurrence-free survival. RESULTS: Median age at diagnosis was 63 years (range, 45 to 86 y) and mean follow-up was 29 months. Patient stratification ASTRO consensus classifications for APBI was 37% suitable, 57% cautionary, and 6% unsuitable. The 3-year breast control rate was 98.7%. Three-year overall recurrence-free survival was 94.4%, and 3-year mastectomy-free survival was 97.4%. Using univariate analysis, no tumor or patient factors were associated with ipsilateral breast recurrence. However, tumor grade (P<0.05), stage (P=0.04), estrogen receptor status (P<0.001), progesterone receptor status (P<0.001), tumor size (P<0.001), and ASTRO suitability criteria (P=0.027) were associated with overall recurrence-free survival. No differences were observed when outcomes of patients with ductal carcinoma in situ were compared with those with invasive disease. CONCLUSIONS: In our high-volume community-based program, APBI outcomes are comparable with those reported from large academic institutions. We also found relationships between tumor stage, grade, negative estrogen receptor status, and ASTRO suitability criteria with overall recurrence rates. The continued careful application of APBI in appropriately selected patients appears warranted until phase III trials comparing this modality to whole-breast irradiation have matured.

Changes in presentation, treatment, and outcomes of adult low-grade gliomas over the past fifty years.

BACKGROUND: To identify changes in patient presentation, treatment, and outcomes of low-grade gliomas (LGGs) over the past 50 years. METHODS: Records of 852 adults who received a diagnosis at Mayo Clinic from 1960 through 2011 with World Health Organization grade II LGGs were reviewed and grouped by those who received a diagnosis before (group I: 1960-1989) and after (group II: 1990-2011) the routine use of postoperative MRI. RESULTS: Median follow-up was 23.3 and 8.7 years for groups I and II, respectively. Patients in group I more often presented with seizures, headaches, sensory/motor impairment, and astrocytoma histology. Over time, more gross total resections (GTRs) were achieved, fewer patients received postoperative radiotherapy (PORT), and more received chemotherapy. Median progression-free survival (PFS) and overall survival (OS) were 4.4 and 8.0 years, respectively. Although PFS was similar, 10-year OS was better in group II (47%) than in group I (33%; P < .0001). Improved PFS in multivariate analysis was associated with group I patients, nonastrocytoma histology, small tumor size, successful GTR, or radical subtotal resection (rSTR), PORT, and postoperative chemotherapy. Factors associated with improved OS in multivariate analysis were younger age, nonastrocytoma histology, small tumor size, and GTR/rSTR. CONCLUSIONS: OS for LGG has improved over the past 50 years, despite similar rates of progression. In the modern cohort, more patients are receiving a diagnosis of oligodendroglioma and are undergoing extensive resections, both of which are associated with improvements in OS. Because of risk factor stratification by clinicians, the use of PORT has decreased and is primarily being used to treat high-risk tumors in modern patients.

Prognostic factors and survival patterns in pediatric low-grade gliomas over 4 decades.

BACKGROUND: This study reports changes in long-term survival after the introduction of modern imaging in pediatric patients with low-grade gliomas (LGGs). METHODS: Records from 351 consecutive pediatric patients diagnosed with LGG between 1970 and 2009 at Mayo Clinic Rochester were reviewed and divided into diagnosis before (group I: 1970 to 1989) and after (group II: 1990 to 2009) postoperative magnetic resonance imaging became regularly used in pediatric LGG. RESULTS: Median progression-free survival (PFS) and overall survival (OS) were not reached. Overall, 10-year PFS was 62% and OS was 90%. On multivariate analysis, improved PFS was associated with gross total resection (GTR; P<0.0001) and postoperative radiation therapy (RT; P<0.0001). In those undergoing less than GTR, PFS was improved with RT, nearing rates of patients receiving GTR (P=0.12). On multivariate analysis, higher OS was associated with GTR (P<0.0001) and pilocytic histology (P=0.03). Group II had fewer headaches, fewer sensory/motor symptoms, less postoperative RT, and more GTRs. OS and PFS were not different between the groups. CONCLUSIONS: This large series of pediatric LGG patients with long-term follow-up found no significant changes in OS or PFS over time. Overall, GTR was associated with improved OS and PFS. RT was associated with an improvement in PFS, with the greatest benefit seen in patients undergoing less than GTR.

Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience from the Mayo Clinic.

OBJECT: Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. METHODS: Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. RESULTS: The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9-416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). CONCLUSIONS: This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

Glioblastoma. Part II: Future directions.

Although uncommon, "brain cancer" is one of the most feared diseases that afflict human beings. While still regarded as one of the most deadly forms of primary malignant brain neoplasm, recent advances in the treatment of Glioblastoma Multiforme (GBM) have offered new hope for patients, families and clinicians. In the first part of this two-part evidence-based review, we focused on the multidisciplinary advances that have established the current standard of care practice in the management of GBM. The second part discusses ongoing research efforts, both ongoing clinical trial efforts as well as some of the newer technologies that are forming the promise of the future.

Glioblastoma: Part I. Current state of affairs.

Although uncommon, "brain cancer" is one of the most feared diseases that afflict human beings. While still regarded as one of the most deadly forms of primary brain neoplasm, recent advances in the treatment of glioblastoma (GBM) have offered new hope for patients, families, and clinicians. In the first part of this two-part review, we will focus on the multidisciplinary advances that have established the current treatment approach in the management of GBM. In the second part of this review, ongoing research will be presented including current clinical trials as well as some of the newer technologies that are forming the promise of the future.

The prognostic importance of pathologically involved celiac node metastases in node-positive patients with carcinoma of the distal esophagus or gastroesophageal junction: a surgical series from the Mayo Clinic.

The management of esophageal cancer with involvement of celiac lymph nodes is controversial. The purpose of this retrospective study was to evaluate the clinical importance of metastases to celiac lymph nodes in patients with carcinoma of the distal esophagus or gastroesophageal junction (GEJ) who undergo surgical treatment with curative intent. We reviewed the medical records of 310 patients who underwent definitive esophagectomy at the Mayo Clinic, Rochester, Minnesota, between 1976 and 1999 for carcinoma of the distal esophagus or GEJ. The disease location was distal esophagus in 163 and GEJ in 147. Fifty-two patients (17%) were found to have celiac node involvement. The survival of these patients was compared with that of 97 N0 patients and 161 N1 patients without celiac node involvement. Squamous cell carcinoma and adenocarcinomas were found in 24% and 76%, respectively. Ivor Lewis esophagectomy was the most common surgical procedure (76%), followed by transhiatal resection (14%) and modified Ivor Lewis procedure (5%). The median number of nodes resected was 15 (range, 2-45). The median survival of the entire group was 18.8 months. The median survival was 48 months (range, 1.6 months-22 years) for N0 patients and 15.9 months (range, 0.03 months-14.4 years) for N1 patients without celiac node disease (P < 0.001). The median survival was 11.7 months (range, 2.2 months-15.7 years) for celiac node-positive patients, and this difference was statistically significant when compared with survival in N0 patients (P= 0.001) but not when compared with that in N1 patients without celiac node disease (P= 0.57). Survival at 3 and 5 years was 61% and 45% for N0 patients, 21% and 9% for N1 patients without celiac node disease, and 18% and 11% for patients with celiac node disease, respectively. At 10 years, 7% of patients with celiac node involvement in their resected specimen were alive. By multivariate analysis, patients with 4 or more positive lymph nodes had the worst prognosis (risk ratio [RR], 2.63; 95% confidence interval [CI], 1.98-3.48), regardless of their location. We concluded that celiac node metastases were not an adverse prognostic indicator in patients with celiac node involvement compared with N1 patients without celiac node disease. Overall, the number of positive nodes, not their location, correlated best with survival. Although median survival was poor, a small number of patients with resected celiac node disease had long-term survival. Patients with undetected celiac node disease at the time of surgical resection who were subsequently found to have celiac node involvement appeared to have a prognosis similar to that of patients with stage III disease. Therefore, treatment with curative intent should be considered for fit patients with celiac node disease.

A multi-institutional acute gastrointestinal toxicity analysis of anal cancer patients treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.

Using previous dosimetric analysis methods, we identified the volume of bowel receiving 30 Gy (V(30)) correlated with acute gastrointestinal (GI) toxicity in anal cancer patients treated with intensity-modulated radiation therapy and concurrent chemotherapy. For V(30)>450 cc and < or =450 cc, acute GI toxicity was 33% and 8%, respectively (p=0.003).

Low-grade gliomas in older patients: long-term follow-up from Mayo Clinic.

BACKGROUND: Low-grade gliomas (LGGs) are uncommon in older patients, and long-term clinical behavior and prognostic factors are not well defined in this group. METHODS: The authors retrospectively searched their tumor registry for the records of adult patients (> or =18 years) diagnosed as having nonpilocytic LGG between 1960 and 1992 at Mayo Clinic. The Kaplan-Meier method was used to estimate progression-free survival and overall survival (OS) in patients aged 55 years and older. RESULTS: Of 314 patients initially identified, 32 were aged at least 55 years, with a median age at diagnosis of 61 years (range, 55-74 years). Median follow-up was 17.3 years for survivors. Operative pathologic diagnoses comprised astrocytoma (n = 22, 69%), mixed oligoastrocytoma (n = 7, 22%), and oligodendroglioma (n = 3, 9%). Gross total resection was achieved in 1 patient, radical subtotal resection in 1, and subtotal resection in 14; 16 patients had biopsy only. Postoperative radiotherapy or chemotherapy was given to 23 (72%) patients and 1 (3%) patient, respectively. Median OS was 2.7 years for all patients: 3 years with resection and 2.2 years with biopsy only (P = .58). The 5- and 10-year OS rates were 31% and 18%, respectively. Factors adversely affecting OS on univariate analysis were enhancement on computed tomography (P < .001) and supratentorial location (P = .03). CONCLUSIONS: This retrospective series of older patients suggests that intracranial LGG in this age group behaves aggressively. Pathologic sampling error failing to recognize higher-grade tumors does not seem to account for these poor outcomes. Aggressive management with maximally safe resection followed by adjuvant therapy should be strongly considered.

Intraperitoneal treatment for peritoneal mucinous carcinomatosis of appendiceal origin after operative management: long-term follow-up of the Mayo Clinic experience.

OBJECTIVE: To determine prognostic factors and the impact of intraperitoneal (IP) treatment after surgical resection of peritoneal mucinous carcinomatosis (PMC) of appendiceal origin. SUMMARY OF BACKGROUND DATA: PMC is a rare, malignant, intra-abdominal neoplasm that produces large amounts of mucin. Patients typically present with diffuse peritoneal disease. After surgical treatment, multiple locoregional recurrences are common; recurrences outside the abdomen are infrequent. Treatment regimens include debulking, radiotherapy with IP radioisotopes, and chemotherapies (IP, systemic, or both). Because reported data are variable and heterogeneous, treatment evaluations are challenging. METHODS: We retrospectively reviewed 115 consecutive patients with PMC who underwent maximal surgical resection with or without postoperative therapy between 1985 and 2000 at Mayo Clinic Rochester. After maximal resection, 37 patients received IP 5-fluorouracil, 35 of whom also received IP chromic phosphate P 32. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. RESULTS: All gross disease was removed in 61% of patients. With a median follow-up of 6.1 years, the median OS was 8.1 years. Median OS for patients receiving versus not receiving IP therapy was 23.5 years versus 7.5 years, respectively. The 5-, 10-, and 15-year OS for those receiving and not receiving IP therapy was 82%, 65%, and 52% versus 60%, 27%, and 15%, respectively. Adverse prognostic factors for OS identified by univariate analysis included partial mucin debulking, adenocarcinoma histology, systemic chemotherapy, diffuse IP disease at presentation, and no IP therapy. On multivariate analysis, diffuse IP disease at presentation and no IP therapy remained significant. A separate analysis was performed for the 70 patients who underwent gross total resection, 51% of whom received IP therapy. Adverse prognostic factors for OS included adenocarcinoma histology, systemic chemotherapy, and no IP therapy. CONCLUSIONS: This large, single-institution, retrospective series with long-term follow-up suggests that IP chromic phosphate P 32 and 5-fluorouracil after maximal surgical resection of PMC of appendiceal origin is associated with improved OS and disease-free survival.

Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by esophagogastrectomy has become the standard of care for patients with locally advanced esophageal cancer. This report analyzes our experience with this treatment approach. METHODS: From January 1998 through December 2003, all patients from a single institution receiving neoadjuvant chemoradiotherapy followed by esophagogastrectomy were reviewed for operative mortality, morbidity, long-term survival, and factors affecting survival. Only patients preoperatively staged with both computed tomographic scans and endoscopic ultrasound were included. RESULTS: There were 162 patients (142 men, 20 women), and the median age was 61 years (range, 22 to 81 years). Histopathology was adenocarcinoma in 143 patients and squamous cell in 19. Pretreatment clinical stage was II in 28 patients (17%), III in 111 (68%), and IV (M1a) in 23 (14%). Ivor Lewis esophagogastrectomy was the most common procedure, occurring in 132 patients. Operative mortality and morbidity was 4.9% and 37%, respectively. Pathologic response was complete in 42 patients (26%), near complete in 27 (17%), partial in 88 (54%), and unresectable in 5 (3%). Five-year survival for overall, complete, near complete, and partial response patients was 34%, 55%, 27%, and 27%, respectively (p = 0.013). Patients whose lymph nodes were rendered free of cancer showed improved overall and disease-free survival compared with patients having persistently positive lymph nodes (p = 0.019). CONCLUSIONS: Esophagogastrectomy after neoadjuvant chemoradiotherapy can be performed with low mortality and morbidity. Patients with complete pathologic response have significantly improved long-term survival compared with patients with near complete and partial responses. Future efforts should be directed at understanding determinants of complete responses.

Intracranial low-grade gliomas in adults: 30-year experience with long-term follow-up at Mayo Clinic.

The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-grade gliomas (LGGs). Records of 314 adult patients with nonpilocytic LGGs diagnosed between 1960 and 1992 at the Mayo Clinic, Rochester, Minnesota, were retrospectively reviewed. The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). Median age at diagnosis was 36 years. Median follow-up was 13.6 years. Operative pathology revealed pure astrocytoma in 181 patients (58%), oligoastrocytoma in 99 (31%), and oligodendroglioma in 34 (11%). Gross total resection (GTR) was achieved in 41 patients (13%), radical subtotal resection (rSTR) in 33 (11%), subtotal resection in 130 (41%), and biopsy only in 110 (35%). Median OS was 6.9 years (range, 1 month-38.5 years). Adverse prognostic factors for OS identified by multivariate analysis were tumor size 5 cm or larger, pure astrocytoma histology, Kernohan grade 2, undergoing less than rSTR, and presentation with sensory motor symptoms. Statistically significant adverse prognostic factors for PFS by multivariate analysis were only tumor size 5 cm or larger and undergoing less than rSTR. In patients who underwent less than rSTR, radiotherapy (RT) was associated with improved OS and PFS. A substantial proportion of patients have a good long-term prognosis after GTR and rSTR, with nearly half of patients free of recurrence 10 years after diagnosis. Postoperative RT was associated with improved OS and PFS and is recommended for patients after subtotal resection or biopsy.

Association between bone marrow dosimetric parameters and acute hematologic toxicity in anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy.

PURPOSE: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V(10) and PBM-V(20)) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. RESULTS: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V(5), V(10), V(15), and V(20) were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V(10), V(15), and V(20) (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). CONCLUSION: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.

Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience.

PURPOSE: To report a multicenter experience treating anal canal cancer patients with concurrent chemotherapy and intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: From October 2000 to June 2006, 53 patients were treated with concurrent chemotherapy and IMRT for anal squamous cell carcinoma at three tertiary-care academic medical centers. Sixty-two percent were T1-2, and 67% were N0; eight patients were HIV positive. Forty-eight patients received fluorouracil (FU)/mitomycin, one received FU/cisplatin, and four received FU alone. All patients underwent computed tomography-based treatment planning with pelvic regions and inguinal nodes receiving a median of 45 Gy. Primary sites and involved nodes were boosted to a median dose of 51.5 Gy. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. All late toxicity was scored using Radiation Therapy Oncology Group criteria. RESULTS: Median follow-up was 14.5 months (range, 5.2 to 102.8 months). Acute grade 3+ toxicity included 15.1% GI and 37.7% dermatologic toxicity; all acute grade 4 toxicities were hematologic; and acute grade 4 leukopenia and neutropenia occurred in 30.2% and 34.0% of patients, respectively. Treatment breaks occurred in 41.5% of patients, lasting a median of 4 days. Forty-nine patients (92.5%) had a complete response, one patient had a partial response, and three had stable disease. All HIV-positive patients achieved a complete response. Eighteen-month colostomy-free survival, overall survival, freedom from local failure, and freedom from distant failure were 83.7%, 93.4%, 83.9%, and 92.9%, respectively. CONCLUSION: Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.

Predictors of tumor control in patients treated with linac-based stereotactic radiosurgery for metastatic disease to the brain.

OBJECTIVE: The objective of this study was to determine predictive factors for local control (LC) of brain metastases (BM) treated with Linac-based stereotactic radiosurgery (LB-SRS). METHODS: Between January 1994 and July 2001, 80 patients (126 BM) underwent LB-SRS. All patients had follow-up imaging with computed tomography (40%) or magnetic resonance imaging (60%). Most patients had either lung (41%) or renal cell (20%) cancer. The median SRS prescription dose was 18 Gy (range, 10-21 Gy). Most patients (86%) also received whole-brain radiotherapy (WBRT). LC was defined as the absence of enlargement of the BM on follow-up scans. Actuarial LC analyses were performed by the method of Kaplan-Meier and compared with the log-rank test. Factors analyzed included histology, volume, prescription dose, maximum and minimum tumor dose, target volume ratio, number of arcs and isocenters, total degrees, and WBRT. Multivariate analysis was accomplished. RESULTS: At a median follow up of 8.8 months, 11 BM failed (8.7%). The 1-and 2-year actuarial LC rates were 88.6% and 77.2%, respectively. The most significant factors correlated with LC were prescription (P = 0.0004) and minimum tumor (P = 0.002) doses, and tumor volume (P = 0.04). On multivariate analysis, the sole factor correlated with LC was minimum tumor dose (P = 0.03). CONCLUSION: Our results confirm that LB-SRS is associated with excellent LC rates in the majority of patients treated. However, particular attention should be given to minimum target dose to ensure optimal outcome.

Intensity-modulated radiotherapy and the Internet.

BACKGROUND: The objective of the current study was to evaluate the content and quality of patient-oriented information regarding intensity-modulated radiotherapy (IMRT) on the Internet. METHODS: IMRT websites were identified by reviewing the first 50 uniform resource locators on 5 search engines using the search terms IMRT and intensity modulated radiation therapy. Each site was evaluated by three observers for informational content, presentation, accuracy, and balance. A score of low, moderate, or high was assigned to each category based on a predefined scoring system. An overall score was assigned to each site, ranging from -35 to 100 points. RESULTS: Seventy-seven patient-oriented IMRT websites were identified (45% private, 21% academic, and 18% commercial). Most sites (58%) had a low level of informational content, with information on fundamental aspects of IMRT planning (target delineation and inverse planning) appearing on < 50% of sites. The most commonly discussed tumors were genitourinary (65%) and head and neck (53%) lesions. Few sites, however, described the potential benefits of IMRT (toxicity and tumor control). Most sites (82%) used patient-appropriate language. False and/or misleading information was seen on 42% of sites and was equally common on academic, private, and commercial sites. Balance statements were present on 24% of sites (most of which were commercial). The median overall score was 20 points (range, -25 to 70 points). The median overall scores for academic, private, commercial, and other sites were 10, 20, 25, and 20 points, respectively (P = 0.26). CONCLUSIONS: In general, the content and quality of patient-oriented information regarding IMRT on the Internet were poor. Patients and their physicians need to be aware of these problems when selecting treatment courses.