Nuclear localization of heparanase 2 (Hpa2) attenuates breast carcinoma growth and metastasis.

Unlike the intense research effort devoted to exploring the significance of heparanase in cancer, very little attention was given to Hpa2, a close homolog of heparanase. Here, we explored the role of Hpa2 in breast cancer. Unexpectedly, we found that patients endowed with high levels of Hpa2 exhibited a higher incidence of tumor metastasis and survived less than patients with low levels of Hpa2. Immunohistochemical examination revealed that in normal breast tissue, Hpa2 localizes primarily in the cell nucleus. In striking contrast, in breast carcinoma, Hpa2 expression is not only decreased but also loses its nuclear localization and appears diffuse in the cell cytoplasm. Importantly, breast cancer patients in which nuclear localization of Hpa2 is retained exhibited reduced lymph-node metastasis, suggesting that nuclear localization of Hpa2 plays a protective role in breast cancer progression. To examine this possibility, we engineered a gene construct that directs Hpa2 to the cell nucleus (Hpa2-Nuc). Notably, overexpression of Hpa2 in breast carcinoma cells resulted in bigger tumors, whereas targeting Hpa2 to the cell nucleus attenuated tumor growth and tumor metastasis. RNAseq analysis was performed to reveal differentially expressed genes (DEG) in Hpa2-Nuc tumors vs. control. The analysis revealed, among others, decreased expression of genes associated with the hallmark of Kras, beta-catenin, and TNF-alpha (via NFkB) signaling. Our results imply that nuclear localization of Hpa2 prominently regulates gene transcription, resulting in attenuation of breast tumorigenesis. Thus, nuclear Hpa2 may be used as a predictive parameter in personalized medicine for breast cancer patients.

Prophylactic breast irradiation reduces background parenchymal enhancement (BPE) on MRI: A secondary analysis.

PURPOSE: We recently showed that prophylactic breast irradiation (PBI) reduces the risk of contralateral breast cancer in BRCA mutation carriers undergoing treatment for early breast cancer. It has been suggested that Background Parenchymal Enhancement (BPE) may be a biomarker for increased risk of breast cancer. METHODS: For participants in the trial we reviewed the MRI prior to enrollment and following radiation treatment and scored the contralateral breast for BPE and density. RESULTS: Significant reduction of BPE was more commonly noted following PBI (p = 0.011) compared to the control group. CONCLUSION: Reduction of BPE by PBI may contribute to its prophylactic effect.

Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11-25 (n = 1037) (TAILORx categorization) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

Oral Bisphosphonates and Improved Survival of Breast Cancer.

Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.Experimental Design: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96, P = 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684-9. ©2016 AACR.

Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma: A Rare Cancer Network study.

OBJECTIVE: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. METHODS: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. RESULTS: All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. CONCLUSIONS: In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.

Management of adenoid cystic carcinoma of the breast: a Rare Cancer Network study.

BACKGROUND: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC. METHODS: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy). RESULTS: With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT. CONCLUSION: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery.

The essential role of radiotherapy in the treatment of Merkel cell carcinoma: a study from the Rare Cancer Network.

PURPOSE: To evaluate the role of postoperative radiotherapy (RT) in Merkel cell carcinoma (MCC). METHODS AND MATERIALS: A retrospective multicenter study was performed in 180 patients with MCC treated between February 1988 and September 2009. Patients who had had surgery alone were compared with patients who received surgery and postoperative RT or radical RT. Local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were assessed together with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. RESULTS: Seventy-nine patients were male and 101 patients were female, and the median age was 73 years old (range, 38-93 years). The majority of patients had localized disease (n = 146), and the remaining patients had regional lymph node metastasis (n = 34). Forty-nine patients underwent surgery for the primary tumor without postoperative RT to the primary site; the other 131 patients received surgery for the primary tumor, followed by postoperative RT (n = 118) or a biopsy of the primary tumor followed by radical RT (n = 13). Median follow-up was 5 years (range, 0.2-16.5 years). Patients in the RT group had improved LRFS (93% vs. 64%; p < 0.001), RRFS (76% vs. 27%; p < 0.001), DMFS (70% vs. 42%; p = 0.01), DFS (59% vs. 4%; p < 0.001), and CSS (65% vs. 49%; p = 0.03) rates compared to patients who underwent surgery for the primary tumor alone; LRFS, RRFS, DMFS, and DFS rates remained significant with multivariable Cox regression analysis. However OS was not significantly improved by postoperative RT (56% vs. 46%; p = 0.2). CONCLUSIONS: After multivariable analysis, postoperative RT was associated with improved outcome and seems to be an important component in the multimodality treatment of MCC.

Physical inactivity as a contributing factor for onset of idiopathic benign paroxysmal positional vertigo.

CONCLUSION: Despite limitations arising from a questionnaire-performed study, it seems that nonspecific physical activity can protect against benign paroxysmal positional vertigo (BPPV), possibly by relocating loosened otoconia from the semicircular canals. OBJECTIVES: Mechanical factors might play a role in the onset of the idiopathic form of BPPV. We performed a structured questionnaire study of physical activity in patients with BPPV and controls. METHODS: Sixty-three consecutive patients with idiopathic BPPV participated in the study. Their mean age was 59.2 ± 14.5 years; 14 were men and 49 were women. Sixty-four age- and sex-matched generally healthy individuals served as controls. Levels of physical activity were assessed by the PASE questionnaire, which consists of 12 items quantifying physical activity during leisure, household, and occupational activities over a 7-day period. RESULTS: The total physical score activity was significantly lower in BPPV patients than in controls. Differences were found mainly in household and leisure activity, while occupational activity was similar in both groups, regardless of gender. Patients older than 60 years had significantly lower PASE scores than controls, whereas patients aged 60 years or younger reported similar physical activity to controls. No differences were found between physical activity scores in different types of BPPV or in patients with a first versus recurrent attack of vertigo.

Germline mutations in BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel.

Three mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT) predominate among high risk breast ovarian cancer Ashkenazi Jewish families, with few "private" mutations described. Additionally, the spectrum of BRCA1 and BRCA2 germline mutations among high risk Jewish non Ashkenazi and non Jewish Israelis is undetermined. Genotyping by exon-specific sequencing or heteroduplex analysis using enhanced mismatch mutation analysis was applied to 250 high risk, predominantly cancer affected, unrelated Israeli women of Ashkenazi (n = 72), non Ashkenazi (n = 90), Moslem (n = 45), Christian Arabs (n = 21), Druze (n = 17), and non Jewish Caucasians (n = 5). All Jewish women were prescreened and did not harbor any of the predominant BRCA1 or BRCA2 Jewish mutations. Age at diagnosis of breast cancer (median ± SD) (n = 219) was 40.1 ± 11.7, 45.6 ± 10.7, 38.7 ± 9.2, 45.5 ± 11.4 ± and 40.7 ± 8.1 years for Ashkenazi, non Ashkenazi, Moslem, Christian, and Druze participants, respectively. For ovarian cancer (n = 19) the mean ages were 45.75 ± 8.2, 57.9 ± 10.1, 54 ± 8, 70 ± 0, and 72 ± 0 for these origins, respectively. Overall, 22 (8.8%) participants carried 19 clearly pathogenic mutations-10 BRCA1 and 9 BRCA2 (3 novel): 3 in Ashkenazim, 6 in 8 non-Ashkenazim, 6 in 7 Moslems, 2 in Druze, and 2 in non Jewish Caucasians. Only three mutations (c.1991del4, C61G, A1708E) were detected in 2 seemingly unrelated families of Moslem and non- Ashkenazi origins. There were no inactivating mutations among 55 Ashkenazi high risk breast cancer only families. In conclusion, there are no predominant recurring germline mutations in BRCA1 or BRCA2 genes among ethnically diverse Jewish and non Jewish high risk families in Israel.

High efficacy of pre-operative trastuzumab combined with paclitaxel following doxorubicin & cyclophosphamide in operable breast cancer.

BACKGROUND: Trastuzumab in combination with adjuvant chemotherapy improves disease free survival and overall survival in HER2 over-expressing breast cancer patients. Data concerning the use of trastuzumab in the neo-adjuvant setting is limited. We aimed to compare outcome of HER2 over-expressing breast cancer patients treated with either standard chemotherapy, consisting of doxorubicin, cyclophosphamide and a taxane to outcome of patients treated with the same chemotherapy regimen with the addition of trastuzumab in concurrence with paclitaxel. METHODS: We conducted a retrospective review of all consecutive HER2 over-expressing breast cancer patients treated at the participating institutions during the study period and received neo-adjuvant therapy. Allocation to trastuzumab was not based on clinical parameters and was approved only by part of the insurers. Clinical and pathological characteristics, as well as response rate and type of surgery were analyzed. RESULTS: Thirty seven patients received chemotherapy alone and 24 patients received chemotherapy and trastuzumab. A similar distribution of age, clinical stage and histology was noted in both groups. The rate of pathological complete response (pCR) was significantly higher among the trastuzumab-treated group compared to chemotherapy-alone group (75 vs. 24% respectively, p=0.0002). pCR in the breast was noted in 18 of 24 (75%) compared to 10 of 36 (28%, p=0.0005) and pCR in the axillary lymph nodes was noted in 19 of 20 (95%) compared to 8 of 28 (29%, p=0.0001), in the trastuzumab group compared to the chemotherapy-alone group respectively. The safety profile was similar between both groups and no clinical cardiotoxicity were noted. CONCLUSIONS: The addition of trastuzumab to standard chemotherapy in the neo-adjuvant setting improves pathological complete response rates in HER2 over-expressing breast cancer patients.

Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN).

OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease. METHODS: A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. RESULTS: Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047). CONCLUSIONS: UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.

Wheat grass juice may improve hematological toxicity related to chemotherapy in breast cancer patients: a pilot study.

Myelotoxicity induced by chemotherapy may become life-threatening. Neutropenia may be prevented by granulocyte colony-stimulating factors (GCSF), and epoetin may prevent anemia, but both cause substantial side effects and increased costs. According to non-established data, wheat grass juice (WGJ) may prevent myelotoxicity when applied with chemotherapy. In this prospective matched control study, 60 patients with breast carcinoma on chemotherapy were enrolled and assigned to an intervention or control arm. Those in the intervention arm (A) were given 60 cc of WGJ orally daily during the first three cycles of chemotherapy, while those in the control arm (B) received only regular supportive therapy. Premature termination of treatment, dose reduction, and starting GCSF or epoetin were considered as "censoring events." Response rate to chemotherapy was calculated in patients with evaluable disease. Analysis of the results showed that five censoring events occurred in Arm A and 15 in Arm B (P = 0.01). Of the 15 events in Arm B, 11 were related to hematological events. No reduction in response rate was observed in patients who could be assessed for response. Side effects related to WGJ were minimal, including worsening of nausea in six patients, causing cessation of WGJ intake. In conclusion, it was found that WGJ taken during FAC chemotherapy may reduce myelotoxicity, dose reductions, and need for GCSF support, without diminishing efficacy of chemotherapy. These preliminary results need confirmation in a phase III study.

Boost radiotherapy in young women with ductal carcinoma in situ: a multicentre, retrospective study of the Rare Cancer Network.

BACKGROUND: Outcome data in young women with ductal carcinoma in situ (DCIS) are rare. The benefits of boost radiotherapy in this group are also unknown. We aimed to assess the effect of boost radiotherapy in young patients with DCIS. METHODS: We included 373 women from 18 institutions who met the following inclusion criteria: having tumour status Tis and nodal status (N)0, age 45 years or younger at diagnosis, and having had breast-conserving surgery. 57 (15%) patients had no radiotherapy after surgery, 166 (45%) had radiotherapy without boost (median dose 50 Gy [range 40-60]), and 150 (40%) had radiotherapy with boost (60 Gy [53-76]). The primary outcome was local relapse-free survival. FINDINGS: Median follow-up was 72 months (range 1-281). 55 (15%) patients had local relapse. Local relapse-free survival at 10 years was 46% (95% CI 24-67) for patients given no radiotherapy, 72% (61-83) for those given radiotherapy without boost, and 86% (78-93) for those given radiotherapy and boost (difference between all three groups, p<0.0001). Age, margin status, and radiotherapy dose were significant predictors of local relapse-free survival. Compared with patients who had no radiotherapy, those who had radiotherapy had a decreased risk of local relapse (without boost, hazard ratio 0.33 [95% CI 0.16-0.71], p=0.004; with boost, 0.15 [0.06-0.36], p<0.0001). INTERPRETATION: In the absence of randomised trials, boost radiotherapy should be considered in addition to surgery for breast-conserving treatment for DCIS.

Reducing malignant ascites accumulation by repeated intraperitoneal administrations of a Viscum album extract.

BACKGROUND: Malignant ascites is a major problem in the management of advanced stages of certain malignancies. The possibility of reducing the accumulation of ascites by intraperitoneal injections of a Viscum album extract (Iscador M) was evaluated. PATIENTS AND METHODS: Twenty-three patients, with end-stage malignancies of varying histology, requiring repeated peritoneal punctures, were eligible for analysis. The time-interval between the first two punctures was measured and defined as the baseline. Following each subsequent puncture, Iscador M 10 mg was injected intraperitoneally. The intervals between later punctures were compared to previous intervals. RESULTS: Following the first injection, the median time-interval between injections increased from 7 to 12 days, reaching 13 days after the second injection. No toxicity was observed. CONCLUSION: This phase II study suggests that installation of Iscador M into the peritoneal cavity may reduce the need for repeated punctures. A randomized trial is needed to confirm these promising preliminary results.

Breast cancer in octogenarians.

BACKGROUND: The number of older cancer patients has increased in recent years. Guidelines for their care are often lacking. Data on the natural course of breast cancer and outcome of therapy in this population are needed. METHODS: The authors undertook a retrospective chart review with complete follow-up of 135 women diagnosed with localized breast cancer at age 80 years or older, who received standard or less than standard local treatment in 2 tertiary centers in Israel between 1991 and 2001. RESULTS: Median age at diagnosis was 83 years. In 60 (44%) patients, initial local treatment consisted of modified radical mastectomy or lumpectomy and axillary dissection followed by radiation therapy [standard local treatment (SLT)]; 75 (56%) patients received less than SLT. Tumors were stage T1-T2 in 90% of cases, 76% of the tumors were hormone-sensitive. Infiltrating duct carcinoma predominated (90 cases), mostly (80 of 90) Grade 2-3. Lymph node metastases were detected in 32 of 73 (44%) patients who underwent axillary lymph node dissection. At a median of 70 months after diagnosis, 18 (13%) patients had disease recurrence, and 34 (25%) had died. Axillary failures were detected only in the less-than-SLT group. This did not indicate worse overall or disease-specific survival. CONCLUSION: Most breast cancer octogenarians in this series lived > 6 years after diagnosis. These data do not support the assumption that breast tumors are histologically more indolent in elderly patients. Less than SLT can be applied to this patient group with somewhat increased axillary failure rates that may be addressed upfront by the sentinel node technique.

The safety of full-dose chemotherapy with secondary prophylactic granulocyte colony stimulating factor (G-CSF) following a prior cycle with febrile neutropenia.

Secondary prophylactic administration of recombinant human granulocyte colony stimulating factor (G-CSF) following an episode of febrile neutropenia is recommended if maintenance of dose-intensity is desired. This policy was adopted in our center in patients treated with an intent for cure or durable complete response. The purpose of this study was to evaluate the safety and feasibility of this policy. Patients in whom neutropenia was associated with a life-threatening infection and those who developed prolonged myelosuppression were excluded. Fifty-one patients who developed febrile neutropenia that required intravenous antibiotics following moderately myelotoxic chemotherapy were included. These patients received the next cycle of the same chemotherapy regime without dose modification but with the support of filgrastim (300 or 480 mg/d sc for at least 10 consecutive days). Diagnoses included lymphoma (n = 19), breast cancer (n = 15), germ cell tumor (n = 7), small-cell lung cancer (n = 5), and other solid tumors (n = 5). The incidence of febrile neutropenia during the first cycle given with filgrastim support (N1) was 8/51 (16%). Intravenous antibiotics were required for 3-7 d (median, 4.5 d). During the following cycle (N2), febrile neutropenia developed in 4/41 (10%) patients. Intravenous antibiotics were given for 2, 4, 5, and 7 d. Other dose-limiting toxicities developed in 1/51 patients who received N1 and in 1/41 patients who received N2. There was no drug-related death associated with either cycle. In conclusion, a policy of full-dose chemotherapy with secondary G-CSF support in patients who develop febrile neutropenia following moderately myelotoxic chemotherapy is relatively safe and feasible.

Definition of postlumpectomy tumor bed for radiotherapy boost field planning: CT versus surgical clips.

PURPOSE: To compare the location and extent of the tumor bed as defined by surgical clips and computed tomography (CT) scans, after lumpectomy, for electron boost planning as part of breast radiotherapy. METHODS AND MATERIALS: Planning CT images of 31 operated breasts in 30 patients who underwent lumpectomy were reviewed. One or more clips were placed in the lumpectomy cavity. Serial CT images were used to measure the depth and transverse and longitudinal dimensions. The area and geometric center of the tumor bed were defined by the clips and CT. RESULTS: The CT and clip measurements were identical for the maximal tumor depth in 27 of 30 patients. The CT bed extended beyond the clips by 0-7 mm medially in the transverse/longitudinal extent (multiclip patients). The median distance between the geometric centers in the coronal plane for the tumor bed center was larger for patients with single clips than for those with multiple clips (p < 0.025). Tumor bed areas in the coronal plane defined by both methods correlated strongly. However, the CT-defined area was larger by 13.9 mm2. The CT bed was more readily visible in patients with a shorter interval between surgery and radiotherapy. CONCLUSION: The maximal depth of the tumor bed was similar using the two methods. The extent and centers of the clip-and CT-determined beds differed significantly. This may indicate an underestimation of the tumor bed as defined by clips only and justifies integration of CT information in boost field planning.