Long-term outcome of conventional radiation therapy for central neurocytoma

The authors report the long-term outcome of conventional radiation therapy (RT) in six cases of central neurocytoma (CN). Between 1985 and 1992, six patients were treated with RT for residual tumors or for prevention of recurrence after surgery. The median follow-up period of radiological and clinical status were 171 (range: 128-229) and 202 months (range: 165-227), respectively. Tumors disappeared in three and reduced in three patients at the last follow-up. One-mortality case due to radiation necrosis and one radiation-induced malignancy occurred. White matter degeneration and cortical atrophy were noticed with slow progression of performance deterioration in two patients. Conventional RT seemed to effectively control residual CN after surgery. However, more sophisticated radiation techniques should be applied to minimize the late sequela.     

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma

INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.     

Risk factors for local recurrences after limb-salvage surgery for high-grade osteosarcoma of the extremities

Background: Improvements in preoperative staging as well as in chemotherapeutic regimens have made limb-salvage surgery a reliable modality of treatment for high-grade osteosarcomas of the extremities, with local recurrences in most series of less than 10% after this type of surgery. The quality of surgical margins and local response to preoperative chemotherapy are known to be the most significant factors in recurrence [1, 8–10, 12], and complications related to the biopsy procedure may also be a significant factor. The study reported here comprised a histopathological analysis of our recurrent cases as part of an effort to identify the impact of each of the factors cited above.Materials and methods: Five hundred fourteen cases of high-grade, non-multicentric osteosarcoma of the extremities were treated at the Istituto Ortopedico Rizzoli between March 1983 and August 1991. In this study we analyzed 23 cases of local recurrence in patients with classic osteosarcoma who underwent limb-salvage procedures.Results: In 15 cases we found correlation between the site of local recurrence and the site where the margins were less than wide. In five cases the recurrence was secondary to complications of the biopsy procedure (hematoma, delayed healing). In one case we suspect a previously undetected skip lesion. In the remaining two cases no clear explanation was found for the recurrence. There was also a statistically significant difference in the time of appearance of recurrences related to the tumor response to chemotherapy.Conclusions: For only two cases of recurrence was there no clear explanation. In one we suspect an undetected skip metastasis, and in the other there were certain factors which may have increased its risk of recurrrence (non diagnostic trochar biopsy followed by an incisional biopsy, fair tumor necrosis, recurrence in a 'problem' anatomical site, i.e., the popliteal space). In the remaining cases the following factors were found to be directly related to the development of a local recurrence: a) the quality of the surgical margins, b) site of the biopsy as well as complications related to the biopsy procedure, c) local response to preoperative chemotherapy.     

Long-term outcome of patients treated by radiation therapy alone for salivary gland carcinomas

PURPOSE: To review a single-institution experience with the management of salivary gland cancers treated by radiation alone. METHODS AND MATERIALS: Between 1960 and 2004, 45 patients with newly diagnosed salivary gland carcinomas were treated with definitive radiation to a median dose of 66 Gy (range, 57-74 Gy). Distribution of T-stage was: 24% T1, 18% T2, 31% T3, and 27% T4. Histology was: 14 mucoepidermoid (31%), 10 adenocarcinoma (22%), 8 adenoid cystic (18%), 4 undifferentiated (9%), 4 acinic (9%), 2 malignant mixed (4%), 2 squamous (4%), and 1 salivary duct carcinoma (2%). No patient had clinical or pathologic evidence of lymph node disease. Median follow-up was 101 months (range, 3-285 months). RESULTS: The 5-year and 10-year rate estimates of local control were 70% and 57%, respectively. A Cox proportional hazard model identified T3-4 disease (p = 0.004) and radiation dose lower than 66 Gy (p = 0.001) as independent predictors of local recurrence. The 10-year overall survival and distant metastasis-free rates were 46% and 67%, respectively. CONCLUSION: Radiation therapy alone is a reasonable alternative to surgery in the definitive management of salivary gland cancers and results in long-term survival in a significant proportion of patients. Radiation dose in excess of 66 Gy is recommended.     

Oncologic outcome of parosteal osteosarcoma

Background This retrospective review evaluated the clinical features and surgical outcomes of parosteal osteosarcoma (POS). Methods Nine patients were surgically treated and followed up. Their mean age was 30.8 years. Clinical information and oncologic outcomes of each case were analyzed. Results Sites of involvement were all in the femur, and all tumors arose from the metaphyseal area of the distal femur. Biopsies for definite diagnoses were performed in just two of the nine cases. Wide resection was applied for all tumors. Surgical evaluations were a 1-cm-wide procedure in six cases and a 2-cm-wide procedure (or more) in three cases. All patients were found to be continuously disease free during the follow-up period of 115.1 months. Conclusion POS showed characteristic findings on radiographic images. Therefore, wide resection without biopsy could be performed in 77.8% (7/9) of the cases. This procedure may contribute to attaining better limb function, because of preventing contamination of healthy surrounding tissue and minimizing the extent of resection. The safety margin was evaluated as a 1-cm-wide procedure. For the choice of reconstruction, indication of autobone grafting (3/9) or total knee replacement (TKR) (6/9) depended on tumor size, location, and shape. With no adjuvant treatments, all cases have shown good clinical courses during the entire follow-up period of about 10 years.     

骨肉瘤基因治疗的研究进展

与手术、化疗等骨肉瘤传统的治疗方法不同,骨肉瘤的基因治疗是通过基因工程的方法逆转癌细胞的恶性状态而达到治疗目的.近年来,有关骨肉瘤基因治疗的研究在基因治疗方法、基因载体、载体导入途径和靶向调控等方面取得了一些进展,基因治疗有望成为一种治疗骨肉瘤较理想的方法.     

Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group's protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs

Background: In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin.Patients and methods: Patients 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously.Results: 171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable.Conclusions: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.     

A pilot study of short-course intensive multiagent chemotherapy in metastatic and axial skeletal osteosarcoma.

BACKGROUND: This pilot study was undertaken to assess the feasibility, toxicity and response to short-course multiagent chemotherapy followed by high-dose chemotherapy (HDC) in patients with poor prognosis osteosarcoma. PATIENTS AND METHODS: A total of 30 patients entered the study. Chemotherapy consisted of four blocks of multiagent chemotherapy administered sequentially over a short period in a dose-intensive manner. This therapy was followed by HDC which consisted of carboplatin at an AUC8 x 3 days, etoposide 400 mg/m(2) x 3 days and cyclophosphamide 60 mg/kg x 2 days. RESULTS: A total of 227 cycles of chemotherapy were administered. The main toxicity (for blocks 1-4) was haematological. There were two treatment-related deaths: one post HDC due to sepsis and one during surgery. High-dose chemotherapy was administered to 11 patients (10 with extremity tumours and only one with a pelvic tumour). Twenty-seven patients underwent surgery to the primary. Histological response was assessed in 23 patients. Seven patients (30%) had >90% necrosis. Eight patients underwent pulmonary metastatectomy. The median survival time for the whole group was 16 months. The 2- and 3-year survival rates were 50% and 21% for those with extremity tumours and 19% and 13% for those with axial skeletal tumours. CONCLUSIONS: Dose-intensive multiagent chemotherapy though feasible in the group of patients with extremity tumours did not significantly improve the treatment outcome compared with conventional relapse therapy. Inferior survival rates in the axial skeletal group are attributed to less intensive treatment and poor local tumour control.     

Long-term outcomes for desmoid tumors treated with radiation therapy

PURPOSE: To evaluate long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT), with or without surgery. METHODS AND MATERIALS: Between 1965 and 2005, 115 patients with desmoid tumors were treated with RT at our institution. The median age was 29 years (range, 8-73 years). Of the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease, and 74 (64%) received combined-modality treatment (CMT) consisting of a combination of surgery and RT (median dose, 50.4 Gy). RESULTS: Median follow-up was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%, respectively. On univariate analysis, LC was significantly influenced by tumor size (< or =5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age (< or = 30 vs. >30 years) (p = 0.02). There was no significant difference in LC for patients treated with RT alone for gross disease vs. CMT. For patients treated with CMT, only tumor size significantly influenced LC (p = 0.02). Patients with positive margins after surgery did not have poorer LC than those with negative margins (p = 0.38). Radiation-related complications occurred in 20 (17%) of patients and were associated with dose >56 Gy (p = 0.001), age < or =30 years (p = 0.009), and receipt of RT alone vs. CMT (p = 0.01). CONCLUSIONS: Desmoid tumors are effectively controlled with RT administered either as an adjuvant to surgery when resection margins are positive or alone for gross disease when surgical resection is not feasible. Doses >56 Gy may not be necessary to control gross disease and are associated with high rates of radiation-related complications.     

Long-term use of combined radiation therapy and hormonal therapy in the management of stage D1 prostate cancer

PURPOSE: To determine tumor response, patterns of relapse, and prognostic indicators in patients followed long-term after combined hormonal radiation therapy of adenocarcinoma of the prostate in men with tumor metastatic to pelvic lymph nodes. METHODS AND MATERIALS: Seventy-nine patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node metastases were treated with combined radiation therapy and hormonal therapy. Of these, 55 patients (70%) had T3 disease, with the remainder having earlier-stage disease; 45 (57%) patients had N2 disease (Whitmore-Jewett staging). No distant metastases were detected at initial staging, and no patient had radiographic or pathologic involvement of the para-aortic nodes. Pelvic lymph nodes were irradiated to a dose 45-54 Gy, and the prostate was irradiated to a dose 65-71.8 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose diethylstilbestrol (DES) (2 patients), orchiectomy (21 patients), luteinizing hormone-releasing hormone agonist (12 patients), or combined androgen blockade (44 patients). Prognostic factors examined included microscopic vs. measurable lymph node involvement, one-sided vs. two-sided disease, T stage, pretreatment PSA, method of androgen blockade, and Gleason score. Log-rank analysis was used to determine statistical significance with respect to overall survival, disease-free survival, clinical freedom from progression, and biochemical freedom from progression; Cox multivariate analysis was employed to determine potential confounders. RESULTS: Median follow-up was 6.7 years. There were 25 recurrences among the 79 patients, including 7 biochemical recurrences without clinical evidence of disease, three local recurrences in the prostate, and distant metastases in 14 patients; 2 patients were deceased, with cause of death listed as prostate cancer, though the location of recurrence was unknown. Patients with biochemical failure before 5 years were more likely to fail distantly, 16% vs. 4% (p < 0.001). Overall actuarial survival at 5, 8, and 12 years was 86%, 72%, and 53%, respectively, whereas actuarial disease-free survival was 90%, 87%, and 81%. Ten patients died of intercurrent disease; these included 4 patients who died of a separate (nonpelvic) malignancy of nonadenocarcinomatous histology with no elevation in PSA. When the potential prognostic variables were examined, a trend toward increased biochemical recurrence in patients with Gleason score >or=8 was observed; this became statistically significant when the 4 patients with known residual lymph node disease after biopsy were excluded (p < 0.03). Gleason score remained the only significant indicator on multivariate analysis. A single long-term toxic event, recto-ureteral fistula, was observed. CONCLUSION: Combined hormonal and radiation therapy continues to represent an effective treatment option for patients with adenocarcinoma of the prostate with metastasis confined to pelvic lymph nodes. All patient groups seem to have a better disease-free survival than that reported previously in single-modality hormone or radiation treatment series. There is a suggestion that patients with lower Gleason score have a lower risk for recurrence. Combined modality therapy may also extend disease-free survival and allow patients to maintain independent function.     

Long-term risk of secondary skin cancers after radiation therapy for Hodgkin’s lymphoma

Purpose

Survivors of Hodgkin’s lymphoma (HL) are at risk of secondary tumors. We investigated the risk of secondary skin cancers after radiotherapy compared to treatment without radiation and to an age-matched population.

Material and methods

We conducted a retrospective cohort study of 889 HL patients treated between 1965 and 2005. Data on secondary skin cancers and treatment fields were retrieved. Incidence rates were compared to observed rates in the Dutch population.

Results

318 skin cancers were diagnosed in 86 patients, showing significantly higher risks of skin cancers, the majority being BCC. The standardized incidence ratio (SIR) of BCC in HL survivors was significantly increased (SIR 5.2, 95% CI 4.0–6.6), especially in those aged <35 years at diagnosis (SIR 8.0, 95% CI 5.8–10.7). SIR increased with longer follow-up to 15.9 (95% CI 9.1–25.9) after 35 years, with 626 excess cases per 10,000 patients per year. Most (57%) skin cancers developed within the radiation fields, with significantly increased risk in patients treated with radiotherapy compared to chemotherapy alone (p = 0·047, HR 2·75, 95% CI 1·01–7.45).

Conclusion

Radiotherapy for HL is associated with a strongly increased long-term risk of secondary skin cancers, both compared to the general population and to treatment with chemotherapy alone.     

Immunosuppression and reconstitution with thymosin after radiation therapy

Since 1976, 102 patients with advanced squamous cell carcinoma, (82, head and neck; 20, esophagus), have been evaluated before receiving irradiation and thymosin fraction 5 therapy at the University of California, San Francisco (UCSF). Thymosin fraction 5 is a mixture of at least 20 polypeptides which has been shown to have immune enhancing capabilities in primary immunodeficiency disease and various malignancies. Immunity prior to treatment (measured by total lymphocyte count, E and EAC rosettes, lymphocyte stimulation with phytohemagglutinin (PHA) and in mixed leukocyte culture (MLC) with allogeneic cells and quantitative serum immunoglobulins) was comparable and normal in the 80 control patients and the 22 thymosin treated patients. Postirradiation significant depression (p < 0.01) was demonstrated in cellular immunity in both groups of patients with decreased T and B cell numbers and depressed PHA and MLC stimulation. To date there have been an equal number of recurrences and deaths in both groups of patients.     

The utility of computed tomography in radiation therapy: an estimate of outcome

Several studies have shown that computed tomography (CT) scanning leads to changes in planned therapy for some 40 to 60 % of patients studied. An empirical model has been developed to estimate the improvement in local control and long term survival attributable to CT. The model is based upon an average dose-response relationship for the tumors and involves a technique for estimating the change in tumor control probability when part of the tumor is underdosed. Using this model, it was estimated that, in one series of patients, CT scanning improved the local tumor control probability by an average of 6 %, and improved the chance of 5-year survival by an average of 3.5 %.     

Management and outcome after local recurrence of osteosarcoma

We report on the management and outcome of 96 patients who developed local recurrence (LR) after having definitive primary treatment with chemotherapy and surgery for non-metastatic osteosarcoma. LR developed at a median of 11 months from initial surgical treatment. 18% of patients had metastases prior to the diagnosis of LR and 23% were found to have metastases synchronously. The prognosis for this group with metastases was 14% survival at 2 years. In the 57 patients without metastases at the time of development of LR, survival was 51% at 2 years and 41% at 5 years. Treatment was by excision of the LR and radiotherapy or by amputation. The only significant prognostic factors identified were the presence of metastases at the time of development of LR (P < 0.0001) and small size of the LR. The role of adjuvant chemotherapy was unclear. Whilst every attempt should be made to avoid LR, patients who develop LR are curable, particularly if they do not have metastases at the time of diagnosis of the LR.     

Ten-year outcome after combined modality therapy for inflammatory breast cancer

PURPOSE: To evaluate the long-term outcome of combined modality therapy for inflammatory breast cancer. METHODS AND MATERIALS: The data from 54 women treated between 1983 and 1996 for inflammatory breast cancer were analyzed. Patients with metastatic disease or disease progression on induction chemotherapy were excluded. Induction chemotherapy was given to 52 patients. Mastectomy was performed in 52 patients. Radiotherapy was delivered to the breast or chest wall and regional lymph nodes in all patients. The median follow-up for all patients was 5.1 years. RESULTS: The 5- and 10-year overall survival rate was 56% and 35%, respectively; the corresponding relapse-free survival rates were 49% and 34%. Patients with a pathologic complete response after chemotherapy with or without preoperative radiotherapy had better 5- and 10-year overall survival rates (65% and 46%, respectively) and 5- and 10-year relapse-free survival rates (59% and 50%, respectively) compared with patients without a pathologic complete response. Those patients had a 5- and 10-year relapse-free survival rate of 45% and 27%, respectively. Locoregional failure at 5 and 10 years was 8% and 19%, respectively. CONCLUSION: The outcomes for patients completing multimodality therapy compare favorably with published data; however, the exclusion of patients with progression during induction chemotherapy may account in part for these results. The pathologic complete response rate was found to be an important prognostic factor. Selected patients with inflammatory breast cancer have the potential for long-term survival.     

Long-term results after intraoperative radiation therapy for gastric cancer

PURPOSE: We retrospectively analyzed the impact of intraoperative radiation therapy (IORT) on long-term survival in patients with resectable gastric cancer. METHODS AND MATERIALS: From 1991 to 2001, a total of 84 patients with gastric neoplasms underwent gastectomy or subtotal resection with IORT (23 Gy, 6-15 MeV; IORT-positive [IORT(+)] group). Patients with a history of additional neoadjuvant chemotherapy, histologically confirmed R1 or R2 resection, or reoperation with curative intention after local recurrence were excluded from further analysis. The remaining 61 patients were retrospectively matched with 61 patients without IORT (IORT-negative [IORT(-)] group) for Union Internationale Contre le Cancer (UICC) stage, patient age, histologic grading, extent of surgery, and level of lymph node dissection. Subgroups included postoperative UICC Stages I (n = 31), II (n = 11), III (n = 14), and IV (n = 5). RESULTS: Mean follow-up was 4.8 years in the IORT(+) group and 5.0 years in the IORT(-) group. The overall 5-year patient survival rate was 58% in the IORT(+) group vs. 59% in the IORT(-) group (p = 0.99). Subgroup analysis showed no impact of IORT on 5-year patient survival for those with UICC Stages I/II (76% vs. 80%; p = 0.87) and III/IV (21% vs. 14%, IORT(+) vs. IORT(-) group; p = 0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT(+) vs. IORT(-) group. Total surgical complications were more common in the IORT(+) than IORT(-) group (44.3% vs. 19.7%; p < 0.05). The locoregional tumor recurrence rate was 9.8% in the IORT(+) group. CONCLUSIONS: Use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in patients with curable gastric cancer.     

Report of four cases with high-grade surface osteosarcoma

High-grade surface osteosarcoma is the rarest of the three types of surface osteosarcoma. Four cases with high-grade surface osteosarcoma arising from the distal femur and tibia are reported in this study. One patient was previously diagnosed with Turner's syndrome. Radiologically, three cases presented characteristic appearances suggesting high-grade bone-forming sarcoma arising from the bone surface; however, one case was similar to other juxtacortical lesions such as periosteal and parosteal osteosarcoma, which typically have a better prognosis than high-grade surface osteosarcoma. Therefore, all cases underwent biopsy to determine a definitive diagnosis. Our strategy of treatment for high-grade surface osteosarcoma was a combination of wide resection and pre-/post-operative chemotherapy, equivalent to the treatment for conventional intramedullary osteosarcoma. At the last follow-up, two cases were still undergoing chemotherapy, one case was continuously disease free during the follow-up period of 81 months, and one patient was living with no evidence of disease 60 months after surgery. The aim of this study is to report the clinical information, oncological outcome and appropriate treatment for high-grade surface osteosarcoma.