Prognostic factors in localized Ewing's tumours and peripheral neuroectodermal tumours: the third study of the French Society of Paediatric Oncology (EW88 study).

PURPOSE: (1) To improve survival rates in patients with Ewing's sarcoma (ES) or peripheral neuroectodermal tumours (PNET) using semi-continuous chemotherapy and aiming to perform surgery in all; (2) To identify early prognostic factors to tailor therapy for future studies. PATIENTS AND METHODS: One hundred and forty-one patients were entered onto the trial between January 1988 and December 1991. Induction therapy consisted of five courses of Cytoxan, 150 mg/m(2) x 7 days, followed by Doxorubicin, 35 mg/m(2) i.v on day 8 given at short intervals. Surgery was recommended whenever possible. The delivery of radiation therapy was based on the quality of resection and the histological response to CT. Maintenance chemotherapy consisted of vincristine + actinomycin and cytoxan + doxorubicin. The total duration of therapy was 10 months. RESULTS: After a median follow-up of 8.5 years, the projected overall survival at 5 years was 66% and disease-free survival (DFS) was 58%. In patients treated by surgery, only the histological response to CT had an influence on survival: 75% DFS for patients with a good histological response (less than 5% of cells), 48% for intermediate responders and only 20% for poor responders (> or = 30% of cells), P < 0.0001. The initial tumor volume by itself had no influence on DFS in these patients. In contrast, the tumour volume had a strong impact on DFS in patients treated by radiation therapy alone. Age had no impact on outcome. CONCLUSION: Therapeutic trials for localized Ewing's sarcoma should be based on the histological response to chemotherapy or on the tumour volume according to the modality used for local therapy.     

Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. One STS patient also received combination chemotherapy. Local control was achieved in nine patients (90%) with a follow-up of 30-119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. Two patients with Ewing's sarcoma relapsed (1 patient with both local and distant failure) at 26 and 58 months and were again rendered disease-free with surgery, total body irradiation and further chemotherapy. One patient relapsed for a second time, being disease-free from the first relapse for 30 months. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.     

Curability of Ewing's sarcoma and considerations for future therapeutic trials

Twenty previously untreated children with primary Ewing's sarcoma and 8 children with primary tumor and metastatic disease were treated with surgery or radiation therapy (6,000-7,000 rads) for their primary tumor and T-2 chemotherapy. Of the 20 children with primary Ewing's sarcoma treated with T-2 "adjuvant" chemotherapy, 15 had no evidence of recurrent disease for from 31+-82+ months (median 46+ months) from the start of treatment. The actuarial 5-year disease-free survival rate for this group of patients was 75%. Eight patients presenting with metastatic disease had complete responses to T-2 chemotherapy, but 7/8 with metastatic disease eventually had tumor recurrence. Examination of the treatment failures, both those patients relapsing after adjuvant chemotherapy for primary Ewing's sarcoma (5), and those relapsing after having a complete response of metastatic disease (7) to T-2 chemotherapy, revealed that all relapses occurred at the end of the second year of T-2 chemotherapy or after chemotherapy was stopped. In addition, of 23 patients receiving "curative" radiation therapy to their primary tumor, 5 had local recurrence (22%) and 6 (26%) had severe functional debility secondary to combined radiation therapy and T-2 chemotherapy. The conclusions drawn from this experience have led us to consider a new approach to the treatment of Ewing's sarcoma, namely: 1) more aggressive initial or "induction" chemotherapy with subsequent T-2 "maintenance" chemotherapy to eradicate more completely all metastatic microfoci of disease presumed to be present in patients with primary tumor at the time of diagnosis, and ostensively present in patients with metastatic disease; 2) the use of surgery alone or in combination with moderate doses of radiation therapy in those patients in whom we can predict a high frequency of local recurrence (pelvic lesions) or a high percentage of "functional failures" (young children with lower extremity lesions). Preliminary results with this latter approach are encouraging with 11/13 patients with primary Ewing's sarcoma free of disease at 12+-26+ months. A longer follow-up of this more aggressive treatment is needed to determine the superiority of this approach for both increased survival and improved late physical rehabilitation.     

Radiation therapy as local treatment in Ewing's sarcoma. Results of the Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86

The Cooperative Ewing's Sarcoma Studies, CESS 81 and CESS 86, are multiinstitutional trials with more than 80 participating institutions from Germany, the Netherlands, Austria, and Switzerland. Treatment consists of four courses of multiagent chemotherapy and local therapy. Local therapy was not randomized and was either radical surgery or resection plus postoperative irradiation or definitive radiation therapy. Here results according to local therapy have been analyzed for 93 protocol patients with localized Ewing's sarcoma (ES) who have been recruited in CESS 81 from January 1981 to February 1985 and 122 protocol patients recruited in CESS 86 from January 1986 to November 1989. The 3-year relapse-free survival (RFS) was 55% in CESS 81 and 62% in CESS 86. In CESS 81, the RFS was better for surgically treated than for irradiated patients. In this study there was an extremely high incidence of local failures (50%) after definitive irradiation. In CESS 86, however, the results after radiation therapy have been improved markedly (3-year RFS 67% after radiation therapy, 65% after surgery, and 62% after resection plus irradiation). Possible explanations for the improvement of radiotherapeutic results are as follows: selections for patients for radiation therapy, start of local therapy, and quality of radiation therapy. In CESS 86, irradiated patients were randomized to receive either conventionally fractionated irradiation with less intense chemotherapy or hyperfractionated irradiation with simultaneous chemotherapy. There was no difference in treatment results at the time of analysis. The authors conclude that selection of patients for local treatment modalities and quality of treatment performance has an impact on local and overall treatment results in ES.     

Prognostic factors in the treatment of Ewing's sarcoma. The Ewing's Sarcoma Study Group of the German Society of Paediatric Oncology CESS 81

From 1981 up to February 1985, a total of 93 protocol patients entered the study CESS 81. The protocol recommended an initial 18-week period of polychemotherapy (VACA) followed by local therapy and two additional cycles of chemotherapy. Local therapy consisted either of radical surgery or of incomplete resection plus postoperative irradiation with 36 Gy or of radiotherapy alone (46 and 60 Gy). Centrally located lesions were always irradiated with 60 Gy. This article summarizes the data after 5 years. Data of 93 patients were analysed in October 1986 after a median follow-up of 37 months. The projected 5-year survival is 50%. The relapse rate was 42%, distant relapses occurred in 19%, local (plus distant) relapses in 23%. Most of the relapses occurred during the first 3 years of observation. Failure rate was high in patients undergoing irradiation alone (44%). Initial tumour mass (greater than 100 ml) and histopathologic response to initial chemotherapy were identified as major prognostic factors. Tumour site and type of local therapy were not significant if patients were categorised by tumour volume. In small lesions, surgery and radiotherapy were equally effective. In large lesions greater than 100 ml volume, a trend towards a better prognosis in surgically treated patients was observed. The results of CESS 81 emphasize the importance of permanent local control in Ewing's sarcoma even in the presence of systemic control by an effective multi-drug chemotherapy.     

Ewing's sarcoma: local tumor control and patterns of failure following limited-volume radiation therapy

Sixty children with localized osseous Ewing's sarcoma were treated between 1978 and 1988 with induction chemotherapy (cyclophosphamide, adriamycin), irradiation and/or surgery, and 10 months of maintenance chemotherapy (cyclophosphamide, adriamycin, dactinomycin, vincristine). Following induction chemotherapy, 43 patients received primary radiation therapy to limited radiation volumes defined by post-chemotherapy residual soft tissue tumor extension and initial osseous tumor extent. Irradiation was defined as low dose at 30-36 Gy (median 35 Gy) for 31 cases with objective response to induction chemotherapy and high dose at 50-60 Gy (median 50.4 Gy) for 12 patients with poor response to induction chemotherapy or with tumors greater than or equal to 8 cm. Overall event-free survival at 5 years is 59% and local tumor control is 68%. Initial failures have been local (12), simultaneous local and distant failures (7), and distant (6). In the surgical resection group, 14 patients had complete resection without radiation therapy, and 3 patients had microscopic residual plus 35-41 Gy; 100% local control has been maintained. In 43 patients with primary radiation therapy group, local tumor control is 58% (p = .004). Despite limited radiation volume, 18/19 local failures occurred centrally within the bone, well within the radiation volume. Imaging response to induction chemotherapy predicted local tumor control in the radiation therapy group: 62% with complete response/partial response versus 17% with no response/progressive disease (p less than 0.01). Local tumor control related strongly to primary tumor size in the radiation therapy group; among 31 cases receiving 35 Gy, local tumor control is 90% for lesions less than 8 cm versus 52% for tumors greater than or equal to 8 cm (p = .054). The central pattern of local failure in this experience suggests the effectiveness of limited radiation volume. The overall local tumor control rate following the tested dose level of 35 Gy appears to be inadequate, although results in selected cases with tumors less than 8 cm in greatest tumor dimension indicate potential efficacy in a yet limited experience.     

Results of initial doxorubicin, 5-fluorouracil, and cyclophosphamide combination chemotherapy for inflammatory carcinoma of the breast

Forty-three patients with nonmetastatic inflammatory breast carcinoma have been treated by initial doxorubicin, 5-fluorouracil, and cyclophosphamide (FAC) combination chemotherapy. After three chemotherapy cycles, responding patients underwent surgery. Chemotherapy was then completed for nine cycles of FAC followed by locoregional radiation therapy. All patients received tamoxifen 40 mg/day for 1 year from the time of diagnosis. Thirty-eight patients (88%) had a clinical response to chemotherapy and underwent surgery. On histologic examination 17 patients had a residual tumor mass less than 1 cm diameter or a complete tumor disappearance; lymph nodes dissection was negative in 15 patients. With a median follow-up of 48 months, the predicted 5-year disease-free survival (DFS) is 48% (median DFS, 46 months). Analysis of prognosis factors shows that age, menopausal status, and histologic grade have no predictive value. The DFS and overall survival were significantly improved by the presence of hormonal receptors and a low number of positive lymph nodes (less than 4) at surgery. The most significant prognosis factor was the residual tumor mass after initial chemotherapy with an 80% predicted 5-year DFS for the responding patients versus 30% for the no responding patients (P less than 0.001).     

No benefit of ifosfamide in Ewing's sarcoma: a nonrandomized study of the French Society of Pediatric Oncology.

PURPOSE: To undertake a new protocol with the goals of improving the chemotherapeutic treatment of pediatric Ewing's sarcoma by introducing ifosfamide, and to widen the indications for surgical resection of Ewing's tumor to obtain better local control and to reduce radiation doses. PATIENTS AND METHODS: The French Society of Pediatric Oncology initiated its first cooperative Ewing's sarcoma study in 1978, using a four-drug regimen (cyclophosphamide, dactinomycin, Adriamycin [doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France], and vincristine). Ninety-five patients were included, and, at 5 years, the disease-free survival reached a plateau of 51%. After encouraging responses of recurrent soft tissue or bone sarcomas to ifosfamide, a second study began in 1984 using a new chemotherapy regimen in which cyclophosphamide was replaced by ifosfamide. Sixty-five patients were treated. RESULTS: By February 1992, the median follow-up was 5.8 years. The estimated 5-year disease-free survival was 52%. We observed unexpected cardiac toxicity. Three patients experienced acute cardiac failure that was lethal in two cases. The acute toxicity of ifosfamide prompted us to stop the protocol. Retrospectively, the lack of efficacy reinforced our decision. CONCLUSION: We conclude that ifosfamide did not improve the outcome of the patients despite the fact that these two treatment regimens were not randomized.     

Preliminary results of treatment of Ewing's sarcoma of bone in children and young adults: six months of intensive combined modality therapy without maintenance

Thirty-one previously untreated patients with Ewing's sarcoma were treated with an intensive chemotherapy program of vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cyclosphosphamide (VADRIAC) in combination with radiation therapy to the primary site (greater than 50 Gy) and bone metastases (45 to 50 Gy). An intensified regimen with one further cycle of chemotherapy (VADRIAC), total body irradiation (TBI), and autologous bone marrow transplantation was given to patients with primary tumors of the pelvis, humerus, femur, and chest wall without metastases and to all patients with metastases at diagnosis. Patients with primary tumors of the distal extremity and other sites without metastases at diagnosis were treated on a less intensive chemotherapy regimen of VADRIAC without the intensification. Therapy was completed within 6 to 7 months in all patients. Thirteen patients had metastatic disease at diagnosis; only two of these had the lung as the sole site of metastatic disease. Eighteen patients had no evidence of metastatic disease at diagnosis: ten of these patients had tumors that arose in central axis and proximal extremity sites, and eight had tumors that arose in distal extremity and other sites. Thirty of the 31 patients achieved a complete remission, although two patients underwent amputation: one before chemotherapy and radiation and one after chemotherapy and radiation because of persistent local disease. Seventeen remain in their first complete remission at a median time on study of 30 months and a median time after completion of therapy of 24 months. Fourteen patients have relapsed (13) or progressed (1): ten in metastatic sites and four in the primary site. One patient had persistent local disease after radiation requiring amputation. Nine of the 13 patients with metastatic disease at diagnosis have relapsed compared with five of the 18 patients without metastatic disease. For the entire group, the actuarial survival is 78% (65% to 87%) at 30 months, and the actuarial disease-free survival is 58% (46% to 69%) at 30 months.     

Staging, therapy and prognosis of primary non-Hodgkin's lymphoma of bone and a comparison of results with localized Ewing's sarcoma: ten years experience at the Istituto Ortopedico Rizzoli

Thirty consecutive cases of localized primary non-Hodgkin's lymphoma of bone (PNHLB) were treated in a 10-year period at the Istituto Ortopedico Rizzoli with localized radiation (4 cases) and localized radiation and adjuvant chemotherapy (26 cases). The doses of radiation varied from 3000-4500 rad. A variety of staging procedures evolving with new diagnostic techniques over the 10 years were performed. Adjuvant chemotherapy comprised two different regimens of vincristine, adriamycin and cyclophosphamide. Twenty-four of the 26 patients (92%) have been free of disease with a median follow-up of 75.5 months (18-144 months). Two patients developed meningeal involvement and one patient, treated with radiation therapy only, developed a local recurrence. The results are compared to the management of 68 Ewing's sarcoma patients treated during the same period. Here, higher doses of localized radiation therapy (approximately 5000 rad) and similar adjuvant chemotherapy were administered. The survival was 32% (22/68) with a higher incidence of local recurrence (21%). These data indicate that PNHLB should be considered a separate entity from Ewing's sarcoma and can be treated successfully with lower doses of radiation to the primary tumor and adjuvant chemotherapy. The observations are also compared to a variety of other biological characteristics of Ewing's sarcoma. Since only two patients developed meningeal relapse, our experience does not permit a firm recommendation for routine prophylactic treatment of the central nervous system in PNHLB.     

Therapy for primary non-Hodgkin's lymphoma of bone and a comparison of results with Ewing's sarcoma. Ten years' experience at the Istituto Ortopedico Rizzoli

The authors report on the results obtained in 30 consecutive cases of primary non-Hodgkin's lymphoma of bone (PNHLB) treated at the Istituto Ortopedico Rizzoli between 1972 and 1982. Four patients were treated with radiotherapy only and 26 were treated with radiotherapy plus adjuvant chemotherapy. At a median follow-up of 86 months (range, 30-160), among the 26 patients treated with chemotherapy also there were 3 relapses (2 had meningeal involvement and 1 had recurrence in another bone). Relapse (local recurrence plus multiple new localizations) was observed in one of the four patients treated with radiotherapy only. These results are compared with the results of 68 patients with Ewing's sarcoma who were treated during the same period with radiation therapy and adjuvant chemotherapy and reported in a previous study. In this group, the disease-free survival rate was only 32% (20/68) with a much higher incidence of local recurrence (31%). The necessity of making a clear distinction between PNHLB and Ewing's sarcoma is discussed.     

Pathological assessment of response to induction chemotherapy in breast cancer

Macroscopic and microscopic pathology review was used to assess the degree of tumor reduction after preoperative chemotherapy in 90 patients with inflammatory and locally advanced breast cancer. Fifteen (17%) patients had no evident residual macroscopic tumor on gross pathological examination, and 6 of these 15 had no residual tumor on microscopic review either. There was no significant difference in disease-free and overall survival between the six patients with no microscopic disease and the nine patients with only microscopic residual disease but no residual macroscopic tumor. These 15 patients with major reduction after induction chemotherapy had a longer disease-free survival (DFS) (median not reached at 5 yr) than the other 75 patients with lesser degrees of tumor reduction (DFS = 22 mo; P less than 0.01). Clinical evaluation of response to chemotherapy was a less accurate predictor of outcome than was the pathological assessment of response. Complete clinical responders had a 4-yr DFS of 55%, whereas patients with non macroscopic residual tumor following preoperative chemotherapy, less than one-half of whom had been judged to be a complete clinical responder, had a median DFS of greater than 60 mo and a 4-yr DFS of 75%. Patients whose mastectomy specimen had no macroscopic residual disease had a 93% 5-yr survival compared to patients with a less marked response to therapy who had a 5-yr survival of 30% (P less than 0.01). No pretreatment patient or tumor-related variables correlated with the degree of tumor reduction following preoperative therapy. Achievement of a mastectomy specimen free of residual macroscopic tumor after preoperative chemotherapy is an excellent prognostic factor for a prolonged DFS and survival. This information should be considered in the selection of postoperative systemic therapy.     

Ewing's Sarcoma of the Head and Neck: A Retrospective Analysis of 24 Cases

Introduction and purpose. Primary Ewing's sarcoma arising from the bones of the head and neck region is extremely rare representing only 1- 4% of all Ewing's sarcoma cases. Previous reports suggest a better prognosis for that particular anatomic site. The purpose of this study was to analyze the clinico-epidemiologic characteristics of that rare clinical presentation, as well as its patterns of failure and prognosis following treatment.Materials and methods. This study included a retrospective review of the medical records of patients with the diagnosis of Ewing's sarcoma of the head and neck region treated at King Faisal Specialist Hospital and Research Center between 1975 and 1996.Results. Out of a total number of 24 cases analyzed, there were 17 males and 7 females with a ratio of 2.4:1. The median age at diagnosis was 16.5 years. A painful swelling was the most common clinical presentation.The maxilla was the most common site of presentation (9/24 cases). There were 3/24 cases who presented with metastatic disease at diagnosis.The majority of patients (16/24 cases) had a tumor size >10 cm. Most patients were treated with systemic chemotherapy plus localized irradiation following an initial biopsy.With a mean follow up of 3.4 years, the 5-year actual overall survival (OS) for the whole group was 53%, while the 5-year actuarial disease-free survival (DFS) was 30%. These figures were higher than those repor ted from our institution for young patients (相似文献   

Outcome analysis for stage IE and IIE thyroid lymphoma

Previous reports have revealed modest results in the management of thyroid lymphoma with radiotherapy alone. This retrospective report evaluates the outcome of patients treated for thyroid lymphoma with radiotherapy alone and with combined modality therapy (chemotherapy and radiotherapy) at a single institution. Twenty-seven patients with stages IE and IIE non-Hodgkin's lymphoma of the thyroid gland were treated between 1960 and 1998 at Barnes-Jewish Hospital, of which 14 patients were stage IE and 13 patients were stage IIE. The median age at diagnosis was 67 years, and there were 21 females and 6 males evaluated. The median follow-up time was 38 months (range: 3-279 months). All patients had histologically proven non-Hodgkin's lymphoma, of which 22 patients (81%) were intermediate grade. Treatment consisted of radiotherapy alone in 19 patients and a combined modality therapy in 8 patients. The median radiation dose to the thyroid bed was 44 Gy, and most patients received a doxorubicin-containing regimen administered prior to radiotherapy. Patient, tumor, and treatment-related characteristics were evaluated using Cox regression analysis. Local-regional tumor control, disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Four patients had local relapse in this series, with a crude local tumor control rate of 85%. No factor was determined to be significant for local tumor control. The actuarial 5-year DFS and OS for the entire cohort were 57%, and 56%, respectively. In terms of DFS, both age and stage were statistically significant. The 5-year actuarial DFS for patients less than age 65 years was 83% versus 37% for those more than this age (p = 0.024). Furthermore, the 5-year actuarial DFS for patients with stage I and II disease was 69% and 45%, respectively (p = 0.022). In multivariate analysis, age continued to be significant for DFS (p = 0.049). Overall survival analysis revealed age, local tumor control, and stage to be significant in univariate analysis. Multivariate analysis was further carried out using Cox proportional hazard model, and it revealed age (p = 0.006) and local tumor control (p = 0.007) to be significant. Primary thyroid gland lymphomas have a favorable outcome with appropriate therapy, but prognosis depends on both clinical stage and age at presentation. Because of the risk of both local-regional and distant failure, combined modality approaches that use chemotherapy with radiotherapy are warranted for intermediate- and high grade thyroid lymphoma.     

Therapy for localized Ewing's sarcoma of bone

Fifty-two previously untreated patients with localized Ewing's sarcoma of bone were treated with nonintensive chemotherapy in combination with surgery or radiation therapy (RT). RT was delivered to limited volumes in a dose dependent on the initial response to induction chemotherapy (30 to 35 Gy v 50 to 55 Gy). Fifty of the 52 patients achieved complete or partial responses with induction chemotherapy, with one nonresponding patient rendered free of tumor with surgery. Fifty patients were evaluable for local control of tumor and overall response to protocol therapy. Seventeen relapses have occurred; three metastatic, four local plus metastatic, and ten local. Two factors predicted worse disease-free survival: high WBC count (P = .03) and size of primary tumor (P = .05). Of the 14 local recurrences, 12 occurred in 28 patients who presented with primary tumors greater than 8 cm in size while only two of 22 patients with lesions less than 8 cm had local recurrence. The Kaplan-Meier estimate of disease-free survival at 3 years is 82% for those with small lesions and 64% for those with larger lesions. Site of primary was of no prognostic value (P = .27). The 5-year survival estimate for all patients is 80% (median time on study, 3.3 years).     

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

BACKGROUND: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.     

Neoadjuvant chemotherapy for locally advanced breast cancer: a single center experience

Neoadjuvant chemotherapy (NAC) is one of the treatment options for patients with locally advanced breast cancer (LABC). Preoperative chemotherapy potentially may reduce the extent of the surgery and offers the opportunity to assess the chemosensitivity of the tumor in vivo. Herein, we evaluated the results of NAC in Turkish LABC patients. We retrospectively analyzed 73 LABC patients. Anthracycline/taxane-based chemotherapy regimens were administered. Patients were stratified according to age, menopausal status, type of surgery, response to the treatment, histopathological properties, and survival. After 3–6 cycles of chemotherapy, patients were re-staged radiologically and surgery was performed in operable patients. Adjuvant chemotherapy was administered as needed. The median age was 45 (29–93) at the time of diagnosis. Sixteen percentage of patients were younger than 35 years of age and 45.2% were premenopausal. Median follow-up time was 20.2 months. Sixty-seven out of 73 patients responded to therapy (89%). Breast conserving surgery was possible in the 15% of the patients. In histopathological analysis, lymph node invasion was detected in 85%. The estrogen (ER) and progesterone (PR) receptor were positive in 78.1% and c-erb-B2 was positive in 17.5% of patients. The median disease-free survival (DFS) was 44 months (SE: 9; %95 CI: 27.1–60.8), overall survival (OS) was not reached at the time of analysis. Three-year DFS and OS were 58% and 91.9%, respectively. In a multivariate Cox regression analyses; no demographic or pathologic prognostic parameter predicted overall survival. In recent years, NAC in breast cancer has become a viable treatment option for patients with LABC. NAC is not commonly applied in Turkey. The response rate to NAC in Turkish breast cancer patients is encouragingly high. Broader efforts should be made to evaluate breast cancer patients preoperatively at tumor boards for proper treatment sequence.     

Long-term results of combined modality therapy in primary bone lymphomas

Purpose: To report the Massachusetts General Hospital experience in the management of patients with primary bone lymphoma (PBL) treated with combined modality therapy (CMT).

Methods and Materials: Records from 37 eligible patients were reviewed. Two patients were treated with complete resection of the tumor, while 35 patients underwent radiation therapy with a median total dose of 54 Gy (range 38.35–66.5). All patients received combination chemotherapy, which contained doxorubicin in 33 cases. We compared the current data with our previous experience in patients treated with local measures only.

Results: Actuarial disease-free survival (DFS) at 5 and 10 years is 78% and 73%, respectively, while overall survival (OS) is 91% and 87%, respectively. No local failures were seen. Pathologic fracture at presentation influenced DFS (p = 0.005) and OS (p = 0.017) adversely. OS was compromised in patients older than 60 years (p = 0.059) and DFS in patients with pelvic primaries (p = 0.015). CMT was associated with improved DFS (p = 0.0008) and OS (p = 0.0001) compared to our historical controls. Ten patients (27%) developed complications requiring orthopedic procedures following completion of therapy at a median of 25.5 months (range 4–228).

Conclusion: Patients with PBL have a favorable outcome with CMT, which appears superior to radiation therapy alone. Late complications can be seen, especially in weight-bearing bones.     

Primary Ewing's sarcoma of the ribs. A report from the intergroup Ewing's sarcoma study

Thirty-six patients with primary Ewing's sarcoma of the ribs have been reviewed. Of these, 21 had clinically localized disease at diagnosis and were entered on protocol IESS 7299, eight had regional and seven metastatic disease at diagnosis and were entered on protocol 7450. The 21 with localized disease were treated with surgical excision or biopsy, followed by local radiotherapy (in all but one patient) and randomization to one of three chemotherapy regimens. Eleven patients (52%) remain disease-free for periods ranging from 18 to 64 months, respectively. Seven of eight patients who underwent complete surgical excision of the primary lesion remain disease-free, compared with four of 12 (excluding one patient who died disease-free) who remain disease-free after partial excision or biopsy. However, analysis of size of tumor at diagnosis reveals that smaller primary tumors have a better prognosis irrespective of extent of surgery. Protocol IESS 7450, consisted of radiotherapy to all areas of known disease and four drug chemotherapy. Four (50%) with regional disease but none with metastatic disease have remained alive and continuously disease-free. It is concluded that an aggressive approach to Ewing's sarcoma of the ribs is justified by the results, as even regional disease may be curable. The apparent prognostic advantage for those patients undergoing surgical excision may be explained by patient selection.     

Intensive systemic chemotherapy in localized Ewing's sarcoma in childhood. A historical trial

To assess the value in Ewing's sarcoma of a new multiagent therapy (vincristine, cyclophosphamide, Adriamycin, (doxorubicin) procarbazine), 30 children with a localized tumor (eight distal, nine proximal, 13 central lesions) treated at the Institut Gustave-Roussy between 1973 and 1976 (E3), were pair-matched by site of primary with 30 control patients treated without intensive chemotherapy between 1967 and 1972 (E1) at the same institution, both groups having the same local radiotherapy. Actuarial survival and disease-free survival rates at six years were significantly higher in E3 at P less than 0.01, respectively, 58% and 49% versus 25% in E1. The prognostic value of the primary site was ascertained only in children under chemotherapy. In this group there were six early relapses with death within 14 months and nine late relapses at 21 to 38 months. Among these nine patients, six died, one is living with disease, and two are currently alive in second remission. Fifteen patients are continuously free of disease 50 to 90 months after first treatment (median, 69 months): functional sequelae are minimal in six, moderate in seven, and severe in two children with limb amputation. It is concluded that in future treatments chemotherapy must be intensified and begun prior to local treatment which has to be reevaluated for radiation modalities and for radical surgery indication.