Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation.

PURPOSE: Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL. METHODS: Open-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov (identifier: NCT01920932). RESULTS: Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy. CONCLUSION: The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.

Nodal Response to Neoadjuvant Chemotherapy Predicts Receipt of Radiation Therapy After Breast Cancer Diagnosis.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved overall survival (OS) in patients with breast cancer, but it is unclear how post-NACT response influences radiation therapy administration in patients presenting with node-positive disease. We sought to determine whether nodal pCR is associated with likelihood of receiving nodal radiation and whether radiation therapy among patients experiencing nodal pCR is associated with improved OS. METHODS AND MATERIALS: Clinical N1 (cN1) female breast cancer patients diagnosed during 2010 to 2015 who were ypN0 (ie, nodal pCR; n = 12,341) or ypN1 (ie, residual disease; n = 13,668) after NACT were identified in the National Cancer Database. Multivariate logistic regression was used to identify factors associated with receiving radiation therapy. Cox proportional hazards modeling was used to estimate the association between radiation therapy and adjusted OS. RESULTS: The study included 26,009 patients; 43.9% (n = 5423) of ypN0 and 55.3% (n = 7556) of ypN1 patients received nodal radiation. Rates of nodal radiation remained the same over time among ypN0 patients (trend test, P = .29) but increased among ypN1 patients from 49% in 2010 to 59% in 2015 (trend test, P < .001). After adjusting for covariates, nodal pCR (vs no stage change) was associated with decreased likelihood of nodal radiation after mastectomy (∼20% decrease) and lumpectomy (∼30% decrease; both P < .01). After mastectomy, nodal (vs no) radiation conferred no significant survival benefit in ypN0 patients, but it approached significance for ypN1 patients (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.69-0.99, P = .04; overall P = .11). After lumpectomy, nodal radiation was associated with improved adjusted OS for ypN0 (HR, 0.38; 95% CI, 0.22-0.66) and ypN1 patients (HR, 0.44; 95% CI, 0.30-0.66; both P < .001), but this improvement was not significantly greater than that associated with breast-only radiation. CONCLUSIONS: ypN0 patients were less likely to receive nodal radiation than ypN1 patients were, suggesting that selective omission already occurs and, in the context of limited survival data, could potentially be appropriate for select patients.

Involved-field irradiation for elderly bladder cancer patients.

OBJECTIVES: Considering that adjuvant radiation therapy is one of the most common treatment methods and the influence of the clinical target volume to treatment-related toxicity, this study aimed to observe the differences in treatment failures about involved-field irradiation (IFI) without lymph node areas versus elective nodal irradiation (ENI) with lymph node areas in elderly patients with bladder cancer. MATERIAL AND METHODS: Ninety-two elderly bladder cancer patients were analyzed from January 2010 to December 2014 in one institution. The primary inclusion criteria were previous after transurethral resection of bladder tumor or partial cystectomy with adjuvant radiotherapy, and the radiation techniques included IFI or ENI. The study required that elderly patients did not received radiotherapy before treatment. We observed treatment-related toxicity and tumor failures, evaluated local progression-free survival, estimated the 3-year overall survival, and analyzed prognostic factors, after IFI and ENI in elderly bladder cancer patients. The outcomes were determined by chi square tests, Kaplan-Meier method and Cox multiple factors analysis. RESULTS: In the experimental group, 42 patients (45.65%) received IFI, and a matched group of 50 patients (54.35%) received ENI. With a median follow-up of 31.47 months (range 4.00-86.00 months), the Kaplan-Meier analysis with a log-rank test demonstrated a statistical difference between the IFI group and the ENI group in acute toxicity (45.23% vs 72.00%, P = 0.008). However, there were no statistical differences in the 3-year overall survival rate (45.20% vs 48.00%, P = 0.860) or the duration of local progression-free survival (24.98 vs 34.30, P =0.729). CONCLUSIONS: IFI is feasible in elderly bladder cancer patients, as shown by a decrease in acute toxicity and no increase in local failure. We need a large number of clinical trials and data to further confirm these results.

Impact of Regional Nodal Irradiation on the Outcomes of N1 Breast Cancer Patients Referred for Adjuvant Treatment: A Patient-Level Pooled Analysis of 2 Clinical Trials.

PURPOSE: To evaluate the impact of regional nodal irradiation (RNI) among N1 operable breast cancer patients who underwent adequate axillary dissection and received adjuvant chemotherapy. PATIENTS AND METHODS: This is a pooled analysis of 812 breast cancer patients referred for adjuvant systemic therapy in 2 prospective randomized studies: NCT00174655 (BIG 02/98) and NCT00312208 (BCIRG005). Overall survival was assessed according to whether patients received supraclavicular and/or internal mammary radiotherapy through Kaplan-Meier estimates. Univariate and multivariate analyses of variables affecting overall and relapse-free survival were performed through Cox regression analysis. Additionally, recurrence rates were analyzed according to regional irradiation patterns. RESULTS: Regional relapse rates (after a median follow-up of 76 months) were 1.5% in both groups of patients who received or did not receive supraclavicular radiotherapy. The risk of regional recurrence was 0.7% in patients who received internal mammary node radiotherapy versus 1.6% in patients who did not receive internal mammary node radiotherapy. The following factors were associated with worse overall survival in multivariate Cox regression analysis: age < 40 years (P < .0001), > T1 stage (P = .003), and negative hormone receptor status (P = .002). Neither supraclavicular nor internal mammary radiotherapy was associated with improvement in overall or relapse-free survival in Cox regression analysis. CONCLUSION: The current analysis does not endorse the routine use of supraclavicular or internal mammary radiotherapy among N1 operable breast cancer patients who have undergone adequate dissection of axillary lymph nodes and who have received standard adjuvant systemic therapy. Given the limited power and potential selection bias of the current analysis, further prospective studies are needed to tackle this research question.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

BACKGROUND: This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). PATIENTS AND METHODS: Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. CONCLUSION: Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.

Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study.

PURPOSE: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. PATIENTS AND METHODS: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: "low risk" (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus "high risk" (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. RESULTS: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. CONCLUSION: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

Stage IB cervix cancer with nodal involvement treated with primary surgery or primary radiotherapy: Patterns of failure and outcomes in a contemporary population.

INTRODUCTION: The purpose of this study is to evaluate patterns of failure, overall survival (OS), disease-free survival (DFS), prognostic factors and late toxicities in node positive International Federation of Gynaecology and Obstetrics (FIGO) stage IB cervix cancer treated with curative intent. METHODS: Patients with FIGO stage IB cervix cancer and positive nodes were identified from the Peter MacCallum Cancer Centre prospective gynaecology database. Patients were treated with primary surgery and adjuvant radiotherapy (S + RT) or primary radiotherapy (primary RT). Prognostic factors examined were tumour size, histology, grade, lymphovascular invasion or corpus uterine invasion, MRI tumour volume, number of nodes involved, highest site of nodal involvement, treatment modality, age and smoking. RESULTS: Of the 103 eligible patients, 43 patients had S + RT and 60 patients had primary RT. Tumours were significantly smaller in the S + RT group (mean 3.0 cm vs. 4.5 cm, P < 0.001). Five-year OS (95% confidence interval) and DFS (95% confidence interval) for the whole cohort was 67.6% (56.5-76.4%) and 66.1% (55.7-74.6%), respectively. Tumour diameter and number of positive nodes were significant prognostic factors for OS and DFS and smoking was related to DFS. Treatment modality was not a significant prognostic factor in OS and DFS. Of 33 patients that relapsed, 32 patients relapsed outside the pelvis. One patient failed in the pelvis only. CONCLUSIONS: Early stage cervix cancer with nodal involvement is associated with excellent pelvic disease control following curative intent treatment. Almost all relapses occurred beyond the pelvis and therefore more aggressive local treatment is unlikely to improve survival in these patients.

Evaluation of the value of ENI in radiotherapy for cervical and upper thoracic esophageal cancer: a retrospective analysis.

BACKGROUND: A retrospective study to compare the failure patterns and effects of elective nodal irradiation (ENI) or involved field irradiation (IFI) for cervical and upper thoracic esophageal squamous cell carcinoma (SCC) patients. METHODS: One hundred and sixty nine patients with the cervical and upper thoracic esophageal SCC were analyzed retrospectively; 99 patients (59%) underwent IFI and 70 patients (41%) received ENI. We defined "Out-PTVifi in-PTVeni metastasis" as lymph node metastasis occurring in the cervical prophylactic field of PTVeni thus out of PTVifi. RESULTS: Out-PTVifi in-PTVeni cervical node metastasis occurred in 8% of patients in the IFI group, all within 2 years after treatment. However, it occurred in 10% of patients in the ENI group, and these failures happened gradually since one year after treatments. No difference was found in OS and the incidences of Grade ≥ 3 treatment-related esophageal and lung toxicities between the two groups. CONCLUSIONS: ENI for cervical and upper thoracic esophageal SCC patients did not bring longer OS and better long-term control of cervical lymph nodes. Although ENI might delay cervical nodes progression in elective field; it could not decrease the incidence of these failures.

Long-term survival outcomes following internal mammary node irradiation in stage II-III breast cancer: results of a large retrospective study with 12-year follow-up.

PURPOSE: To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. METHODS AND MATERIALS: Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. RESULTS: The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. CONCLUSIONS: Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.

Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy.

PURPOSE: To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy. METHODS AND PATIENTS: This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. Randomization was stratified by tumor location (medial/central or lateral), axillary lymph node status, and adjuvant therapy (chemotherapy vs no chemotherapy). The prescribed dose of irradiation to the target volumes was 50 Gy or equivalent. The first 5 intercostal spaces were included in the IMN target volume, and two-thirds of the dose (31.5 Gy) was given by electrons. The primary outcome was overall survival at 10 years. Disease-free survival and toxicity were secondary outcomes. RESULTS: T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group (P=.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 [only for medial/central] or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival. CONCLUSIONS: In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population.

Total gross tumor volume is an independent prognostic factor in patients treated with selective nodal irradiation for stage I to III small cell lung cancer.

PURPOSE: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. METHODS AND MATERIALS: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). RESULTS: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ± 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. CONCLUSIONS: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.

Does the intent to irradiate the internal mammary nodes impact survival in women with breast cancer? A population-based analysis in British Columbia.

PURPOSE: To determine the value of the intent to include internal mammary nodes (IMNs) in the radiation therapy (RT) volume for patients receiving adjuvant locoregional (breast or chest wall plus axillary and supraclavicular fossa) RT for breast cancer. METHODS AND MATERIALS: 2413 women with node-positive or T3/4N0 invasive breast cancer, treated with locoregional RT from 2001 to 2006, were identified in a prospectively maintained, population-based database. Intent to include IMNs in RT volume was determined through review of patient charts and RT plans. Distant relapse free survival (D-RFS), breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the two groups. Prespecified pN1 subgroup analyses were performed. RESULTS: The median follow-up time was 6.2 years. Forty-one percent of study participants received IMN RT. The 5-year D-RFS for IMN inclusion and exclusion groups were 82% vs. 82% (p = 0.82), BCSS was 87% vs. 87% (p = 0.81), and OS was 85% vs. 83% (p = 0.06). In the pN1 subgroup, D-RFS was 90% vs. 88% (p = 0.31), BCSS was 94% vs. 92% (p = 0.18), and OS was 91% vs. 88% (p = 0.01). After potential confounding variables were controlled for, women who received IMN RT did not have significantly different D-RFS (hazard ratio [HR] = 1.02 (95% confidence interval [CI], 0.84-1.24; p = 0.85), BCSS (HR = 0.98 (95% CI, 0.79-1.22; p = 0.88), or OS (HR = 0.95; 95% CI, 0.78-1.15; p = 0.57). In the pN1 subgroup, IMN RT was associated with trends for improved survival that were not statistically significant: D-RFS (HR = 0.87; 95% CI, 0.63-1.22; p = 0.42), BCSS (HR = 0.85; 95% CI, 0.57-1.25; p = 0.39), and OS (HR = 0.78; 95% CI, 0.56-1.09; p = 0.14). CONCLUSIONS: After a median follow-up time of 6.2 years, although intentional IMN RT was not associated with a significant improvement in survival, this population-based study suggests that IMN RT may contribute to improved outcomes in selected patients with N1 disease.

Whole-pelvis or bladder-only chemoradiation for lymph node-negative invasive bladder cancer: single-institution experience.

PURPOSE: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard bladder preserving option for patients with invasive bladder cancer. The standard practice is to treat elective pelvic lymph nodes, so our aim was to evaluate whether bladder-only (BO) CCRT leads to results similar to those obtained by standard WP-CCRT. METHODS AND MATERIALS: Patient eligibility included histopathologically proven muscle-invasive bladder cancer, lymph nodes negative (T2-T4, N-) by radiology, and maximal transurethral resection of bladder tumor with normal hematologic, renal, and liver functions. Between March 2005 and May 2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120 patients) and BO-CCRT (110 patients). Data regarding the toxicity profile, compliance, initial complete response rates at 3 months, and occurrence of locoregional or distant failure were recorded. RESULTS: With a median follow-up time of 5 years (range, 3-6), WP-CCRT was associated with a 5-year disease-free survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5). The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT, respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP-CCRT and 51% for BO-CCRT (p = 0.8). CONCLUSION: BO-CCRT showed similar rates of bladder preservation, disease-free survival, and overall survival rates as those of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node-negative bladder cancer to minimize the side effects of CCRT.

Feasibility of involved-field conformal radiotherapy for cervical and upper-thoracic esophageal cancer.

BACKGROUND: The aim of this study was to investigate the feasibility of involved-field irradiation (IFI) for the treatment of cervical and upper-thoracic esophageal cancer with concurrent chemoradiation. PATIENTS AND METHODS: 102 eligible patients with cervical or upper-thoracic esophageal cancer were treated with concurrent chemoradiation and randomized to either an IFI or elective nodal irradiation (ENI) group. RESULTS: Adverse events included infection (27.4 vs. 64.7%) and nausea (25.4 vs. 54.9%), with a statistically significant difference between the IFI and the ENI group (p = 0.008 and 0.028, respectively). No difference was seen for late radiation reaction. The cumulative incidence of local/regional failure (13.7 vs. 17.6%) and regional lymph failure (7.8 vs. 9.8%) showed no statistically significant difference between the IFI versus the ENI group (p = 0.837 and 0.837, respectively). A nodal out-field relapse rate of only 2% was seen in the IFI group. 3-year survival rates for the ENI and IFI group were 41.3 and 32.0%, respectively (p = 0.58), and 3-year local control rates were 85.7 and 80.1%, respectively (p = 0.34). CONCLUSION: IFI was acceptable for cervical and upper-thoracic esophageal cancer with a decrease in acute toxicities and no increase in lymph node failure.

Esthesioneuroblastoma: is there a need for elective neck treatment?

PURPOSE: To assess the risk of cervical lymph node metastases after definitive treatment for esthesioneuroblastoma (ENB) that did not include elective neck therapy. METHODS AND MATERIALS: This was a retrospective analysis of 26 ENB patients treated at the University of Michigan between 1995 and 2007. Tumor stage was Kadish A in 1 patient, B in 19, C in 5, and unknown in 1. Craniofacial or subcranial resection was performed in 24 patients (92%), with negative margins in 22 (92%). Postoperative radiotherapy (RT) to the primary site was given in 12 patients (46%), and 14 patients (54%) had surgery alone. All patients had clinically N0 disease, and no patient underwent elective neck dissection or radiation. Median follow-up was 72 months. RESULTS: Local relapse-free survival was significantly better for patients who received postoperative RT compared with those who had surgery alone: 100% vs. 29% at 5 years, respectively (p = 0.005). Five-year disease-free survival was 87.5% in the RT group vs. 31% in the surgery-alone group (p = 0.05). Regional failure was observed in 7 patients (27%), 6 with Kadish Stage B and 1 with Stage C disease. The most common site of nodal failure was Level II, and 3 patients failed in the contralateral neck. Only 3 patients with regional failure were successfully salvaged. CONCLUSION: The high rate of regional failures when the neck is not electively treated justifies elective nodal RT in patients with both Kadish Stages B and C. In addition, our experience confirms the beneficial effect on local control of adjuvant RT to the tumor bed.

Is regional lymph node irradiation necessary in stage II to III breast cancer patients with negative pathologic node status after neoadjuvant chemotherapy?

PURPOSE: Neoadjuvant chemotherapy (NAC) generally induces significant changes in the pathologic extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation (LNI) in breast cancer (BC) patients with pathologic N0 status (pN0) after NAC and breast-conserving surgery (BCS). METHODS AND MATERIALS: Among 1,054 BC patients treated with NAC in our institution between 1990 and 2004, 248 patients with clinical N0 or N1 to N2 lymph node status at diagnosis had pN0 status after NAC and BCS. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival (LRR-FS), disease-free survival (DFS), and overall survival (OS). RESULTS: All 248 patients underwent breast irradiation, and 158 patients (63.7%) also received LNI. With a median follow-up of 88 months, the 5-year LRR-FS and OS rates were respectively 89.4% and 88.7% with LNI and 86.2% and 92% without LNI (no significant difference). Survival was poorer among patients who did not have a pathologic complete primary tumor response (hazard ratio, 3.05; 95% confidence interval, 1.17-7.99) and in patients with N1 to N2 clinical status at diagnosis (hazard ratio = 2.24; 95% confidence interval, 1.15-4.36). LNI did not significantly affect survival. CONCLUSIONS: Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among cN0 to cN2 breast cancer patients with pN0 status after NAC. These results need to be confirmed in a prospective study.

Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation.

PURPOSE: To retrospectively evaluate the efficacy of total lymphoid irradiation (TLI)-based reconditioning regimens in patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation. METHODS AND MATERIALS: The results of 14 patients (7 adults and 7 children) with a variety of hematologic malignant diseases treated with a TLI-based reconditioning regimen with 7-Gy single-dose application plus anti-T-lymphocyte antibody OKT3 (n = 11) and/or antithymocyte globulin (n = 7)/fludarabine (n = 9), followed by an infusion of peripheral blood stem cells (n = 13) or bone marrow stem cells (n = 1) from related or unrelated donors, were retrospectively analyzed. RESULTS: Of the 14 recipients, the data from 11 were evaluable for engraftment after TLI-based reconditioning because 3 adults died early (at Day 2, 5, and 15) after the second transplantation of infectious complications. Engraftment in 4 adults was seen after a median of 12 days (range, 10-18) and occurred after a median of 10 days (range, 9-32) in the 7 children. TLI-based reconditioning was well-tolerated with no severe toxicity. The median overall survival and disease-free survival for the whole cohort was 140 days (range, 5-1,268). After a median follow-up of 681 days, the disease-free survival and overall survival rate was 85.7% and 85.7%, respectively, in the children. Despite engraftment in the 4 remaining adults, 1 died of fatal graft-vs.-host disease, 1 of infectious complications, 1 of disease relapse, and 1 of acute respiratory distress syndrome. CONCLUSIONS: In patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation, TLI-based reconditioning regimens allow sustained engraftment, paralleled by a favorable toxicity profile, potentially leading to long-term survival.