Absence Of Radiotherapy Research Articles

Abstract P1-15-03: Eight-Year Update of a Prospective Study of Wide Excision Alone for Ductal Carcinoma In Situ (DCIS) of the Breast

Abstract Background: The need for radiation therapy (RT) in conservatively managed DCIS is a source of ongoing debate. This is an updated analysis of a phase II prospective study of wide excision alone for DCIS. The study was activated in May 1995 and closed in July 2002 following accrual of 158 patients because the number of local recurrences (LR) met the predetermined stopping rules. The objective of the analysis is to update the distribution and cumulative incidence of events (LR, contralateral breast cancer [CBC], second malignancy and death from other causes). Materials and Methods: A total of 158 patients had DCIS with predominant nuclear grade 1 or 2, a mammographic extent of ≥2.5 cm, and excision with final microscopic margins of ≥1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The results presented are from the 8-year analysis (8-year minimum potential follow-up time). Twenty-six patients without recurrence who were followed less than 8 years were excluded from the analysis as were 7 first events (4 LR) that occurred beyond 8 years of follow-up; the analysis thus includes 132 patients and 36 first events. Cumulative incidence curves were generated to assess the rates of LR or other events. Median follow up time was 10 years. Results: Overall, 36/132 patients (27%) had a first event as of April 2010. Of these 36 events, 19 were LR, 13 were CBC, 1 was a second malignancy, and 3 were deaths from other causes. Of the 19 LR, 13 (68%) were DCIS only and 6 (32%) were invasive. Fourteen occurred in the same quadrant and 5 were elsewhere in the ipsilateral breast. The 8-year estimated cumulative incidence of LR was 14.4% (95% CI: 8.4-20.4%). For all other events, the 8-year estimated cumulative incidence was 12.9% (95% CI: 3.6-13.1%). The estimated annual percentage rates of LR, CBC, and other events were 2.1%, 1.5% and 0.4%, respectively. Discussion: The results of this prospective study demonstrate a substantial and ongoing risk of LR and CBC in patients with small, nuclear grade 1 or 2 DCIS treated with wide excision with margins of ≥1cm in the absence of RT. Most LRs occurred in the same quadrant, rather than elsewhere in the breast, suggesting that excision alone is inadequate even for this highly selected population. Further study is warranted to determine if there is a subgroup of DCIS patients with nuclear grade 1 or 2 disease who are at low enough risk of LR following wide excision that RT can be omitted safely. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-15-03.

Deep circumflex iliac artery flap combined with a costochondral graft for mandibular reconstruction

Our aim was to use the deep circumflex iliac artery (DCIA) flap together with a costochondral graft as a safe and reliable bone flap for routine reconstruction of the mandibular body and the temporomandibular joint (TMJ). Five patients with benign tumours of the mandible had segmental mandibulectomy including the condyle, and this was reconstructed in one stage using the DCIA combined with a constochondral graft. The rib was inserted into the iliac crest as a whole transplant, and fixed to the proximal stump of the mandible with a prebent reconstruction plate according to a computer-aided design. The grafts healed uneventfully, and dental implants were inserted in 4 cases. During the 2-year follow-up these patients had good mandibular function, including mouth opening, force of bite, and occlusion. The radiographs showed good bony consolidation between the graft and the stump of the mandible and function of the TMJ. A DCIA flap combined with a costochondral graft is a safe and reliable way to provide not only a large bulk of bone to suit the mandible, but also good function of the TMJ in the absence of radiotherapy.

Neoadjuvant chemotherapy followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for Stage IB2-IIB cervical cancer—Irinotecan and platinum chemotherapy

Objective To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer. Methods Forty-six consecutive patients with stage IB2-IIB cervical cancer were treated with NAC followed by radical hysterectomy plus postoperative chemotherapy. Median (range) body mass index (BMI) of the patients was 20.2 (16.2–26.4). Regimens for NAC and postoperative chemotherapy were irinotecan and cisplatin (CPT-11/CDDP) or CPT-11 and nedaplatin (CPT-11/NDP). A total of six cycles of NAC and postoperative chemotherapy were prescribed. No use of radiotherapy was scheduled, except in the case of a recurrence. Results With a median follow-up period for survivors of 38.8 months (range 24–54 months), the 2- and 3-year progression-free survival rates were 91.2% and 86.1%, respectively. Overall response rate of NAC was 80.4%. Recurrence was observed in seven patients. In the absence of radiotherapy, pelvic recurrence was observed in only three patients; another two had para-aortic lymph nodes and the remaining two distant metastases. Toxicities due to chemotherapy were generally tolerable. Postoperative complications included urinary fistula (four patients, 8.7%) and bowel obstruction (two patients, 4.3%), all of which required surgical intervention. Conclusion The results indicate that NAC followed by surgery plus postoperative chemotherapy but no radiotherapy offers a viable option in the treatment of stage IB2-IIB cervical cancer. Although a relatively large incidence of postsurgical complications was observed among low-BMI patients, this treatment offers the advantage of minimizing radiation-induced morbidity, allowing radiotherapy to be reserved for the possible event of pelvic recurrence.

Atypical Teratoid or Rhabdoid Tumors: Improved Outcome With High-dose Chemotherapy

To retrospectively review an institutional experience in managing atypical teratoid/rhabdoid tumors (AT/RT) of the Central Nervous System with high-dose chemotherapy in infants and children less than 4 years old. Eight AT/RT patients were identified during the study period 2003 to 2008. Tumor location was supratentorial in 3 cases, infratentorial in 3 cases, and multifocal in 2 patients. Five patients presented with leptomeningeal dissemination. Two of these patients did not receive any active therapy. After surgery, the 6 remaining patients received induction therapy followed by sequential high-dose chemotherapy with autologous stem cell rescue. Two patients receive focal irradiation. At a median follow-up of 52 months, 4 patients are alive without evidence of tumor. Three of these patients, including 2 with metastatic disease were not irradiated. However, all surviving patients exhibit neuro-cognitive impairment, either at baseline assessment or upon follow-up. This experience confirms that a subset of young AT/RT patients may achieve long-term survival with intensive and high-dose chemotherapy. The role of radiotherapy is still unclear. However, evidence of neuro-cognitive impairment even in the absence of radiotherapy in this young population suggests that systematic introduction of radiotherapy in current protocols should be carefully assessed.

Male breast cancer: 22 case reports at the National Hospital of Niamey- Niger (West Africa)

Male breast cancer (MBC) is rare. The objective of the study is to report clinicopathological characteristics, treatment patterns, and outcomes of MBC. This study, which includes two parts (retrospective and prospective), focused on all hospitalized male patients with breast cancer during 17 years (1992-2008) with histological confirmation. The series included 22 patients. The mean age was 52.8 years (range: 28-80 years). MBC represented 5.7% of all breast cancers. Most patients had an advanced disease with skin ulceration and inflammation T3 (31.9%) and T4 (59.1%). The majority of patients came from rural areas (63.6%). The duration of signs ranged from 1 to 7 years. Histology found infiltrating ductal carcinoma in 14 cases (63.6%), sarcoma in 3 cases (13.6%), papillary carcinoma in 2 cases (9%), and lobular carcinoma, medullar carcinoma, and mucinous carcinoma in 4.6% each of the others cases. The treatment had consisted of a radical mastectomy (Halsted or Patey) in 19 cases (86.4%) with axillary clearance and incomplete resection in 3 cases (13.6%). In the retrospective study follow-up of 14 patients, we lost sight of 13 patients 6 months after surgery. In the prospective study of 8 patients 10 to 36 months after mastectomy, 4 patients were deceased (50%), 4 were alive with 1 case having a local recurrence and pulmonary metastasis. The advanced clinical forms of MBC are most frequent with skin ulceration and nodal enlargement. The absence of radiotherapy and the low access of chemotherapy limited the treatment to radical mastectomy (Halsted) in the majority of cases.

Monotherapy with methotrexate for primary central nervous lymphoma has single agent activity in the absence of radiotherapy: a single institution cohort

We have retrospectively reviewed toxicities and response of a cohort of primary central nervous system lymphoma (PCNSL) patients treated with high dose parenteral methotrexate (MTX) monotherapy without whole brain radiation. From The Massachusetts General Hospital (MGH) Cancer Registry, active since 1946, we selected all immunocompetent patients with histologic and/or radiographic PCNSL diagnosed between 1980 and 2007. We identified the recipients of MTX with leucovorin rescue as sole therapy. No patient received radiation therapy (XRT). We analyzed this cohort for toxicity, response and patterns of recurrence. The cohort of 121 patients received on average 11 cycles of intravenous MTX at a median dose of 8 g/m2. Median interval between cycles was 10 days. After 3 months of therapy, the overall response rate was 85% (58% CR, 27% PR). The overall survival (OS) for the cohort was 7 years and progression-free survival (PFS) was 3.14 years. A trend toward a higher PFS was seen in patients who continued to receive MTX (3.48 years) every three months as compared to patients who ceased MTX after one year (2.86 years). Of 68 patients who achieved initial CR, there were 40 recurrences. Twenty-six of the 40 were re-induced with MTX as above; Sixty-nine percent again achieved CR. Eighty-one treatment-related toxicities occurred in 1316 MTX cycles. These toxicities included MRI white matter changes (N = 8) and lead to MTX cessation in 16 patients. High-dose MTX monotherapy of PCNSL is well-tolerated and provides PFS of >3 years and OS >7 years.

Male breast cancer: 22 case reports at the National Hospital of Niamey, Niger

BACKGROUND: Male breast cancer (MBC) is rare. The objective of the study is to report clinicopathological characteristics, treatment patterns, and outcomes of MBC. METHODS: This study, which includes two parts (retrospective and prospective), focused on all hospitalized male patients with breast cancer during 17 years (1992–2008) with histological confirmation. RESULTS: The series included 22 patients. The mean age was 52.8 years (range: 28–80 years). MBC represented 5.7% of all breast cancers. Most patients had an advanced disease with skin ulceration and inflammation T3 (31.9%) and T4 (59.1%). The majority of patients came from rural areas (63.6%). The duration of signs ranged from 1 to 7 years. Histology found infiltrating ductal carcinoma in 14 cases (63.6%), sarcoma in 3 cases (13.6%), papillary carcinoma in 2 cases (9%), and lobular carcinoma, medullar carcinoma, and mucinous carcinoma in 4.6% each of the others cases. The treatment had consisted to a radical mastectomy (Halsted or Patey) in 19 cases (86.4%) with axillary clearance and incomplete resection in 3 cases (13.6%). In the retrospective study follow-up of 14 patients, we lost sight of 13 patients 6 months after surgery. In the prospective study of 8 patients 10 to 36 months after mastectomy, 4 patients were deceased (50%), 4 were alive with 1 case having a local recurrence and pulmonary metastasis. CONCLUSION: The advanced clinical forms of MBC are most frequent with skin ulceration and nodal enlargement. The absence of radiotherapy and the low access of chemotherapy limited the treatment to radical mastectomy (Halsted) in the majority of cases.

A Multicenter Retrospective Analysis of Survival Outcome Following Postoperative Chemoradiotherapy in Non–Small-Cell Lung Cancer Patients With N2 Nodal Disease

To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non-small-cell lung cancer (NSCLC) with N2 lymph node involvement. This study included 183 patients from four centers in southwest China who underwent radical section of Stage III-N2 NSCLC without any preoperative therapy. One hundred and four were treated with POCRT and 79 with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 48 and 54 Gy), whereas the cycles of platinum-based chemotherapy ranged from two to six with a median of four. The median duration of follow-up was 72 months. The 5-year overall survival rate (OS) was 30.5% in the POCRT group, and 14.4% in the POCT group (p = 0.007). The 5-year disease-free survival rate (DFS) was 22.2% in POCRT group and 9.3% in POCT group (p = 0.003). In a multivariate analysis, N1 nodal involvement (N1+/N2+) was associated with significantly worse OS (HR = 1.454, 95% CI, 1.012-2.087, p = 0.043) and DFS (HR = 1.685, 95% CI, 1.196-2.372, p = 0.003). Absence of radiotherapy and treatment with fewer than three cycles of chemotherapy both were poor prognostic factors for both OS and DFS. As compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected Stage III-N2 nodal disease in NSCLC. Future study of treatment modality with radiotherapy and chemotherapy is warranted, especially focusing on both N1 and N2 nodal status.

Nasopharyngeal carcinoma in sub-Saharan Africa: a tribute to Mr. Peter Clifford

Poorly differentiated nasopharyngeal carcinoma (NPC) is a major malignancy in certain areas of Asia. It exists also in Africa, notably among largely Arab populations in North Africa, and in "hotspots" in East Africa among "native" Africans. This article deals with the latter, as studied and defined in depth during the 1960s and 70s by the Irish-born surgeon, Peter Clifford. Through his published works, he has influenced and helped define the field of head and neck cancer as it exists in Kenya. He also did pioneering work on the African childhood malignancy, Burkitt's lymphoma (BL). Both BL and NPC have been ultimately shown to be associated with the human herpes Epstein-Barr virus (EBV). This article is written as a tribute to Peter Clifford, focusing on his work on NPC, where he first defined the disease "hotspots" in the Kenyan Highlands, studied how best to treat the malignancy in the absence of radiotherapy, looked at possible NPC predisposing factors in the Kenyan setting, and ultimately addressed how the cancer cells interact with EBV. Peter Clifford's pioneering work was cut short by accident. Although outside East Africa he remains largely an 'unsung hero' in the field, his influence has been great. It begs to be re-addressed and reconsidered.

Adjuvant radiotherapy use in a population-based sample of breast cancer patients

617 Background: Previous studies have suggested underutilization and socioeconomic disparities in use of adjuvant radiotherapy (RT) among patients with breast cancer. However, these studies used registry data which may be incomplete. Methods: We evaluated data from 2260 survey respondents with nonmetastatic breast cancer, aged 20–79 years, diagnosed from June 2005-February 2007 in Detroit and Los Angeles and reported to SEER registries (72% response rate). Survey responses regarding treatment and sociodemographic factors were merged to SEER data. Rates of RT receipt were based on patient report. Patients were divided into 3 populations: DCIS pts undergoing breast conservation (BCS), invasive pts undergoing BCS, and invasive pts undergoing mastectomy. These were then stratified based on recurrence risk in the absence of RT (3 groups based on tumor size and grade for DCIS pts, 2 groups separating pts over 70 with Stage I, ER+ tumors from others undergoing BCS for invasive disease, and 3 groups based on tumor size and nodal status for those undergoing mastectomy for invasive disease). Results: Among 306 pts undergoing BCS for DCIS, 85.6% received RT (77.9% of pts at low recurrence risk, 84.8% at intermediate risk, and 95.8% at high risk). Among 1018 pts undergoing BCS for invasive disease, 93.6% received RT (83.6% of low-risk patients and 94.9% of others). Among 661 pts undergoing mastectomy for invasive disease, 39.3% received RT (81.5% of pts at high-risk, 44.5% at intermediate-risk, and 12.1% at low risk). In separate multivariate logistic regression models including risk grouping and sociodemographic variables for each population, there were no significant associations between RT receipt and race, education, or income. Among pts receiving RT, delay was reported by 15.9% of the DCIS group, 19.5% of those treated for invasive disease after BCS, and 27.4% of those treated for invasive disease after mastectomy. Conclusions: RT use is high after BCS with little evidence of socioeconomic disparities. But lower than optimal rates after mastectomy even among patients with high expected benefit suggest lingering barriers to effective treatment in these patients. Less RT use in patients with lower expected benefit suggests that legitimate clinical uncertainty influences decision-making. No significant financial relationships to disclose.

Pineal gland tumors: experience from the SEER database.

Pineal gland tumors are rare and account for less than 1% of all primary brain tumor diagnoses. They are more commonly seen in pediatric patients than in adults. We analyzed the available SEER data on pineal gland tumors that were diagnosed during the period 1973-2005. The cohort was subdivided into groups on the basis of tumor histology: germ cell tumors, pineal parenchymal tumors, gliomas, and other pineal tumors. Analyses of incidence, survival, factors influencing survival, and treatment modalities are provided. Among the 633 patients with pineal tumors, male sex was predominant, i.e., sex ratio was 3:1 for the whole group and 11.8:1 for those with germ cell tumors. The 5-year overall survival (OS) for the cohort was 65% +/- 2.1%. Those with germ cell tumors experienced the best survival (OS = 78.9% +/- 2.3%), followed by those with gliomas (OS = 61% +/- 9.3%), and those with pineal parenchymal tumors (OS = 47.2% +/- 4.2%). Non-germ cell tumors, absence of radiotherapy from treatment regimen, and diagnosis before 1993 were the only factors associated with a negative impact on survival. The extent of surgical tumor resection did not affect survival in any histologic subgroup. We conclude that, although pineal tumors are histologically diverse, they share some similarities due to their unique location. An aggressive surgical approach should be considered with caution in this region. Further studies on different pineal tumors subtypes are needed.

Can Radiotherapy Affect the Apical Sealing Ability of Resin-Based Root Canal Sealers?

The authors conducted a study to assess the influence of radiotherapy on the apical sealing ability of one recently introduced resin-based root canal sealer and two sealers that have been in use for several years. The authors divided 90 human maxillary anterior teeth into three groups according to the type of root canal sealer used and, using lateral condensation, obturated the roots with gutta-percha. They randomly divided all roots into two main groups according to the presence or absence of radiotherapy. For the groups that received irradiation, a dose of 60 gray was delivered in fractions of 1.8 Gy per day, five days a week for seven weeks. The authors then performed the centrifuging dye penetration test to determine apical leakage for each specimen. The authors compared the specimens in the groups that received radiotherapy after endodontic treatment with the specimens in the groups that did not undergo radiotherapy after endodontic treatment. They found that mean apical leakage was slightly higher in the radiotherapy groups, but they did not observe any statistical difference between the groups (P > .05). In the groups that did not undergo radiotherapy, the mean apical leakage for the specimens in the MM-Seal (MicroMega, Besançon, France [not marketed in the United States]), AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany) and AH 26 (Dentsply DeTrey GmbH) groups was 2.52 +/- 0.42 millimeters, 2.85 +/- 0.52 mm and 3.73 +/- 0.41 mm, respectively. In the groups that underwent radiotherapy, the mean apical leakage for the specimens in the MM-Seal, AH Plus and AH 26 groups was 2.72 +/- 0.55 mm, 2.96 +/- 0.47 mm and 3.93 +/- 0.61 mm, respectively. The apical sealing ability of the resin-based root canal sealers decreased slightly when radiotherapy was administered, although there was no statistically significant difference. Clinicians can safely use a resin-based root canal sealer in patients receiving radiotherapy.

Postoperative Adjuvant Chemotherapy for Node-Positive Cervical Adenocarcinoma

We examined the effectiveness of postoperative adjuvant chemotherapy for node-positive cervical adenocarcinoma. During the period from 1994 to 2002, 98 consecutive patients with clinical stage I and II cervical adenocarcinoma were treated surgically without having undergone any prior treatment. Surgical procedures included radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Postoperatively, 21 patients were found to have lymph node metastasis, and all were treated with chemotherapy in the absence of radiotherapy. All patients were followed up for at least 5 years. Recurrence developed in 9 of the 21 patients, all 9 died of the disease. Six of the 9 recurrences were extrapelvic lesions. Five-year disease-free survival and overall survival were 57% and 67%, respectively. Recurrence was more common in patients with 6 or more positive nodes than in those with fewer than 3 positive nodes. These data suggest the potential role of postoperative chemotherapy for treatments of cervical adenocarcinoma. However, the effectiveness of chemotherapy alone in node-positive cervical adenocarcinoma was likely not as high as that in squamous cell carcinoma. Despite our use of postoperative chemotherapy in the absence of pelvic radiation, the disease recurred predominantly at distant sites.

Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose

Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

Surgical Efficiency or Eradication Sufficiency

The management of local and early mucosal cancer of the esophagus is an enormous challenge. There is a change in the practice developing with the establishment of endoscopic mucosal resection and other ablative techniques. Das et al. in this issue have used the Surveillance Epidemiology and End Results (SEER) database of the National Cancer Institute data to compare survival of 99 patients treated using endotherapy (endoscopic mucosal resection, thermal ablation, and photodynamic therapy), with 742 patients treated with surgical resection. Using the Cox proportional hazards model, there was no survival difference between the groups. The survival predictors were the age at diagnosis and the absence of radiotherapy. Although many patients are unsuitable for surgical excision and are offered alternative therapy, these data provide evidence that endotherapy may be an equally effective alternative for many patients with early esophageal cancer. It supports the need for randomized data where this can be achieved. These population-based data open up the possibility of wider acceptance of endoscopic techniques.

Brain stem metastases treated with radiosurgery: prognostic factors of survival and life expectancy estimation

Background The objective of this study is to study prognostic factors of survival and 3 stratification systems for life expectancy estimation in patients with brain stem metastases treated with radiosurgery. Methods Between December 1999 and November 2006, 25 patients with 27 brain stem metastases were treated with Gamma Knife radiosurgery. The lesions' mean volume was 0.6 mL (0.013-3.6 mL). The mean marginal dose was 20 Gy (15-24 Gy). Univariate and multivariate studies were done to identify prognostic factors, and 3 patient stratification systems were applied for survival estimation: RPA, SIR, and BSBM. Results The primary tumor location was in the lungs in 12 patients, breast in 8, and other in 5. Fourteen lesions were located in the pons, 9 in the midbrain, and 4 in the medulla. All patients were followed clinically. Radiologic follow-up was available in 21 lesions (78%). Tumor control was achieved in all but one followed lesion (95%). There were no complications related to treatment. Median survival of patients with brain stem metastases was 11.1 months. In multivariate analysis, KPS of 80 or more, control of the primary tumor, absence of radiotherapy, and a marginal dose higher than 18 Gy were associated with better survival. The BSBM in the univariate and multivariate analyses was the strongest predictor of survival ( P < .0001). Conclusions The BSBM was the most useful tool for estimating survival. Rather than the brain stem location of an intracranial metastasis, the patient integral clinical status seems to be more important in determining survival.

Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy

IntroductionSome patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.MethodsWe performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.ResultsWithin the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).ConclusionA highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.

Angiosarcoma Arising in an Unirradiated Breast with Subsequent Pituitary Metastasis

Angiosarcoma of the breast is a rare condition with known risk factors. The Stewart-Treves syndrome describes angiosarcoma of the arm or breast in the setting of adjuvant radiation therapy (RT) after breast conservation surgery. Angiosarcoma of the breast, in the absence of RT, is rarer still. We present a unique case of angiosarcoma of the breast, diagnosed 6 years after conservative surgery for carcinoma of the breast when no adjuvant RT was given. Chronic postoperative lymphoedema in the breast delayed the investigation of skin changes, with an eventual diagnosis of angiosarcoma. An isolated pituitary metastasis 9 months from the diagnosis, the first such reported case, adds to the complexity of the case. The diagnosis and management of angiosarcoma of the breast is discussed. Angiosarcoma is a rare occurrence after breast conservative surgery. Postoperative lymphoedema can impede early diagnosis. The disease can display unique metastatic potential

The cephalic and external jugular veins: Important alternative recipient vessels in left‐sided microvascular breast reconstruction

The internal mammary and thoracodorsal vessels are the standard recipient sites in microsurgical breast reconstruction. We review our series of venous outflow alternatives when these vessels are inadequate or unusable. A retrospective review of all free breast reconstructions was performed from July 2003 through December 2005. Outcomes were measured with regard to re-exploration, flap failure, and fat necrosis, with attention to the timing and side of reconstruction, as well as the presence or absence of radiation therapy. A total of 141 free breast reconstructions were performed during the study period. In seven cases (5%), alternative venous outflow vessels were selected (cephalic or external jugular vein). Nine anastamotic complications occurred, all of which involved the left internal mammary group (statistically significant for venous thrombosis, P = 0.0063) and three flaps failed. All cephalic and external jugular veins remained patent with no flap failures or fat necrosis within this group. The cephalic vein and external jugular vein are excellent alternatives for venous outflow in free breast reconstruction if neither the internal mammary nor thoracodorsal veins are sufficient, especially in left-sided reconstruction.

Dactinomycin‐Induced, Severe Lichenoid Eruption in a Child

There is little information in the medical literature about skin rashes associated with dactinomycin in the absence of radiotherapy. We report a 12-month-old male child who developed a severe cutaneous reaction that consisted of a widespread pruritic papular eruption associated with fever and a poor general state after dactinomycin administration. Skin biopsy specimen findings confirmed the diagnosis of lichenoid eruption. The rash improved with topical steroid treatment and completely resolved within 1 month with persistence of a residual mild hyperpigmentation. Dactinomycin administration was discontinued for the remaining cycles of chemotherapy.