Prognostic factors and outcome of pelvic, sacral, and spinal chondrosarcomas: a center-based study of 69 cases

BACKGROUND: The surgical treatment of chondrosarcoma of the pelvis, sacrum, and spine is complex and technically demanding. As such, adequate surgical margins have been difficult to achieve, resulting in poor local control and survival. The objective of this study was to assess the outcome of patients with chondrosarcomas in these sites who were treated at a tumor center by using modern, aggressive surgical techniques and to identify prognostic factors. METHODS: Sixty-nine consecutive patients with chondrosarcoma of the pelvis (46 cases), sacrum (11 cases), and mobile spine (12 cases) who were treated at Sahlgrenska University Hospital from 1967 to 1999 were included in this study. Demographic information and follow-up data were obtained and statistically analyzed. RESULTS: There were 53 men and 16 women with a mean age of 45 years and a mean tumor size of 12 cm. There were 61 conventional chondrosarcomas, Grades 1-3 (with 13 arising in a preexisting osteochondroma) and 8 Grade 4 chondrosarcomas (7 dedifferentiated and one mesenchymal). The overall local recurrence rate was 27%, and the estimated overall 5- and 10-year survival rates were 72% and 67%, respectively. In contrast, the observed local recurrence rate was 3% (1 patient) in 31 patients whose conventional chondrosarcomas were resected with adequate surgical margins; 90% of these patients survived and most of them (26 of 31 or 84%) were continuously disease free. Significant factors associated with a worse prognosis with respect to local control and/or survival were high histologic tumor grade, increasing patient age, primary surgery outside of a tumor center, incisional biopsy versus a noninvasive diagnostic procedure, and inadequate surgical margins. CONCLUSIONS: Center-based diagnosis and treatment using modern aggressive surgical techniques significantly improve the prognosis of patients with chondrosarcoma of the pelvis, sacrum, and spine.     

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS : Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.     

The role of preoperative radiotherapy in nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery

PURPOSE: To assess the role of preoperative radiotherapy in patients with nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery and to compare the response of neoadjuvant therapies, local control, and survival with the literature results. METHODS AND MATERIALS: Forty-six patients with osteosarcoma of the limbs who were treated within a limb salvage protocol including preoperative radiotherapy and chemotherapy between 1987 and 2002, were retrospectively analyzed. Median age was 17 years (range, 14-66 years). Treatment was started with neoadjuvant chemotherapy. Cisplatin, epidoxorubicin, ifosfamide, and methotrexate were used in different combinations. Preoperative radiotherapy was applied, usually between the second and third cycle of chemotherapy. Radiotherapy was given (35 Gy in 10 fractions) to 44 patients. Two patients were treated with 46 Gy at 2 Gy/day. Definitive surgery was administered after the third course of chemotherapy. Chemotherapy was complete 6 courses postsurgery. RESULTS: Median follow-up time was 44 months (range, 2-154 months). Forty-four patients had limb-sparing surgery, whereas 2 had amputation. Tumor necrosis rate was >/=90% in 87% of the patients (Huvos Grade 3-4). Two patients had local failures, and 26 patients (56.5%) had distant metastases. The 5-year local control and overall survival rates were 97.5% and 48.4%, respectively. On univariate analysis, age 相似文献   

Stereotactic radiosurgery for intracranial chondrosarcoma

To assess outcomes after stereotactic radiosurgery (SRS) for chondrosarcomas of the skull base, we reviewed 22 patients with cranial base chondrosarcomas who underwent SRS between 1987 and 2009. The median patient age was 42 years (range, 15-75). The median SRS target volume was 8.0 cc (range, 0.9-28.2) and median margin dose was 15.0 Gy (range, 10.5-20). 15 patients (68 %) underwent one or more tumor resections and 3 of these patients also had fractionated radiation therapy. At a median follow-up of 75 months after SRS, seven patients died due to tumor progression. The actuarial overall survival after SRS for the entire group of chondrosarcoma patients was 95, 76, 70 and 56 % at 1, 3, 5 and 10 years, respectively. Factors associated with longer survival after SRS included patient age >40 years, a shorter interval (<6 months) between diagnosis and SRS, and either no or a single prior resection. Treated tumor control rates were 91, 72, 72 and 54 % at 1, 3, 5 and 10 years, respectively. Factors associated with longer progression-free survival after SRS included patient age >40 years and no prior RT. Symptomatic adverse radiation effects occurred in two patients (10 %). Stereotactic radiosurgery may provide a benefit to patients as either a primary or adjuvant therapy. The ability to achieve tumor control in patients with chondrosarcoma is likely to be enhanced by earlier timing of SRS after diagnosis and multimodal management, beginning with resection when feasible followed by early SRS for progressive residual tumor.     

Chondrosarcoma of the phalanx: a locally aggressive lesion with minimal metastatic potential: a report of 35 cases and a review of the literature.

BACKGROUND: Enchondroma is the most common primary benign bone tumor of the hand, especially the phalanges, whereas chondrosarcoma is uncommon at this site. Although phalangeal chondrosarcoma may have ominous histologic features, its biologic behavior is relatively indolent. METHODS: Thirty-five cases of phalangeal lesions previously diagnosed as chondrosarcoma were studied. Histologic and tumor-biologic parameters (Ki-67 and p53 immunohistochemistry) were investigated and correlated with clinical behavior. RESULTS: All cases were characterized by unequivocal malignant histologic features (Grade 2 or higher) or Grade 1 malignant histologic features combined with the presence of cortical destruction and soft tissue extension. The median age of the patients at the time of diagnosis was 67 years (range 21-87 years), with a slight female predominance. Occurrence in the hand was more common than in the foot, with the proximal phalanx affected most often. Treatment varied from local therapy (curettage or local excision) in 16 patients to amputation or exarticulation in 19 cases. Follow-up ranged from 8-432 months for 28 patients. Ten of 15 tumors treated by local therapy recurred whereas none of 13 tumors treated by radical surgery recurred. The median survival was 20.8 years; none of 28 patients developed metastases nor died of disease. Both the type of treatment and localization in the proximal phalanx were associated independently with local recurrence. CONCLUSIONS: Phalangeal chondrosarcoma behaves as a locally aggressive lesion and, in contrast to chondrosarcomas located elsewhere, rarely metastasizes. Treatment is indicated only because of its locally destructive growth. The authors believe that given the excellent survival data, curettage with adequate follow-up should be considered as the treatment of choice if technically feasible, especially in those cases in which amputation would lead to a significant loss of hand function.     

Advanced chondrosarcomas: role of chemotherapy and survival

BackgroundThere are limited data about the role of chemotherapy in patients withadvanced chondrosarcomas.MethodsThe medical charts of 180 patients with advanced chondrosarcomas having received chemotherapy in 15 participating institutions between 1988 and 2011 were reviewed.ResultsMedian age was 52 years. Sixty-three percent of patients had conventional chondrosarcoma and 88% had metastatic disease. Combination chemotherapy was delivered in 98 cases (54.5%). One hundred and thirty-one patients (73%) received an anthracycline-containing regimen. Using RECIST, the objective response rate was significantly different according to histological subtype, being 31% for mesenchymal chondrosarcoma, 20.5% for dedifferentiated chondrosarcoma, 11.5% for conventional chondrosarcoma and 0% for clear-cell chondrosarcoma (P = 0.04). Median progression-free survival (PFS) was 4.7 months [95% confidence interval (CI) 3–6.5]. Performance status (PS) ≥2, number of metastatic sites ≥1 and single-agent regimen were independently associated with poor PFS. Median overall survival (OS) was 18 months (95% CI 14.5–21.6). PS, number of metastatic sites and palliative surgery were independently associated with OS.ConclusionsConventional chemotherapy have very limited efficacy in patients with advanced chondrosarcoma, the highest benefit being observed in mesenchymal and dedifferentiated chondrosarcoma. These data should be used as a reference for response and outcome in the assessment of investigational drugs in advanced chondrosarcoma.     

Bone sarcomas associated with Ollier's disease

Of 55 patients with Ollier's disease seen at the Mayo Clinic between 1907 and 1985, 16 had malignant bone neoplasms: 12 chondrosarcomas, two dedifferentiated chondrosarcomas, one chordoma, and one osteosarcoma. One patient had a chondrosarcoma in two different bones. These findings suggest that approximately 30% of patients with Ollier's disease will develop a malignant bone neoplasm, most probably chondrosarcoma. The prognosis for most patients is good. Five of the 16 patients survived more than 13 years after treatment.     

Extraskeletal myxoid chondrosarcoma: a Multi-Institutional Study of 42 Cases in Japan

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm. Despite a consensus for the distinct clinicopathologic entity of EMC, its clinical features remain controversial. In addition, most studies have contained a small number of patients who underwent definitive surgical treatment. METHODS: Forty-two cases of EMC, which had been identified from files of eight affiliated hospitals and confirmed for histologic diagnosis at the Pathology Center, were analyzed for histologic grade, demographics, treatments, outcomes, and prognostic factors. The average follow-up period was 7.4 years. RESULTS: Included in the study were 20 men and 22 women with a mean age at diagnosis of 52.1 years. The tumors were located mainly in the lower extremities (69%). Thirty-three tumors (79%) were classified as Grade 1 and nine as Grade 2 according to the modified French System. Overall survival was 100% at 5 years and 88% at 10 years. Disease-free survival was 45% at 5 years and 36% at 10 years. Inadequate initial surgery was defined as a significant risk factor for local recurrence by univariate analysis of all 42 patients but not by the analysis of those 30 patients who had undergone wide tumor excision or amputation. Wide excision led to the recurrence rate of 14%. CONCLUSIONS: These findings supported the role of wide excision in the local control of EMC, irrespective of the previous excision procedure or recurrence. The protracted clinical course of the tumors and the presence of patients who had distant metastasis develop after definitive surgery of the primary tumor represented EMC as intermediate malignancy.     

Carbon ion radiotherapy of skull base chondrosarcomas

PURPOSE: To evaluate the effectiveness and toxicity of carbon ion radiotherapy in chondrosarcomas of the skull base. PATIENTS AND METHODS: Between November 1998 and September 2005, 54 patients with low-grade and intermediate-grade chondrosarcomas of the skull base have been treated with carbon ion radiation therapy (RT) using the raster scan technique at the Gesellschaft für Schwerionenforschung in Darmstadt, Germany. All patients had gross residual tumors after surgery. Median total dose was 60 CGE (weekly fractionation 7 x 3.0 CGE). All patients were followed prospectively in regular intervals after treatment. Local control and overall survival rates were calculated using the Kaplan-Meier method. Toxicity was assessed according to the Common Terminology Criteria (CTCAE v.3.0) and the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) score. RESULTS: Median follow-up was 33 months (range, 3-84 months). Only 2 patients developed local recurrences. The actuarial local control rates were 96.2% and 89.8% at 3 and 4 years; overall survival was 98.2%at 5 years. Only 1 patient developed a mucositis CTCAE Grade 3; the remaining patients did not develop any acute toxicities >CTCAE Grade 2. Five patients developed minor late toxicities (RTOG/EORTC Grades 1-2), including bilateral cataract (n = 1), sensory hearing loss (n = 1), a reduction of growth hormone (n = 1), and asymptomatic radiation-induced white matter changes of the adjacent temporal lobe (n = 2). Grade 3 late toxicity occurred in 1 patient (1.9%) only. CONCLUSIONS: Carbon ion RT is an effective treatment for low- and intermediate-grade chondrosarcomas of the skull base offering high local control rates with low toxicity.     

Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute

PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy. RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS: Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome.     

基于SEER数据库绘制列线图分析软骨肉瘤患者预后相关因素

目的:分析软骨肉瘤流行病学特征及影响预后的相关因素,并且绘制列线图来个体化预测患者远期生存率。方法:收集SEER数据库2004至2015年诊断的1 453例软骨肉瘤患者的临床数据,回顾性分析软骨肉瘤患者流行病学特征及影响患者预后的相关危险因素,使用随机数字表法将所有纳入对象以7∶3分为建模组（1 017例）和验证组（436例）并构建列线图进行内部验证,预测软骨肉瘤患者3年、5年的生存率,使用多因素COX风险比例模型来确定独立因素,采用一致性指数(C-index)及校准曲线评估该预测模型的准确性。结果:软骨肉瘤患者男女性别比为:1.23∶1,年龄≥50岁患者占比为55.7%,最常见的发病部位是下肢骨,多因素分析提示,影响软骨肉瘤患者预后的因素包括年龄、性别、肿瘤原发部位、肿瘤大小、病理分级、AJCC TNM分期、手术方式、是否化疗、肿瘤大小;建模组与验证组1、3、5年ROC曲线AUC值分别为:0.87、0.838、0.807,0.864、0.754、0.755;列线图C-index指数为:0.805。结论:列线图可以准确预测软骨肉瘤患者生存率,具有较好的预测精度,有助于对患者进行个性化的预后评估和指导临床决策。     

Chimiothérapie de rattrapage par gemcitabine et docétaxel dans les sarcomes. étude rétrospective monocentrique de 14 observations

Abstract

The sequential combination of gemcitabine (G) followed by docetaxel (D) is one of the rescue options for the treatment of recurrent soft tissue sarcomas in case of failure of a first-line chemotherapy with anthracyclines and ifosfamide. It has also been proposed for relapsed or refractory bone sarcomas.

Patients and Methods

This retrospective study included 14 patients of age 31 to 61 years receiving G (675 mg/m² intravenously in 90 minutes on days 1 and 8) and D (75?C100 mg/m² intravenously on day 8 in 60 minutes) with cycles of 21 days. 5 patients had locoregional relapse, and 9 patients hadmetastatic disease of a variety of bone and soft tissue sarcomas. The performance status (PS) was 0?C1 and most of the patients had received at least 2 previous lines of chemotherapy. The response has been assessed with RECIST criteria, every 2 to 3 cycles.

Results

Among the 5 locoregional relapses of soft tissue sarcomas, 2 partial responses (in 2 high-grade undifferentiated pleomorphic sarcoma) have been observed and 2 stable diseases for more than 6 months. Complete remission persists in 3 cases (after subsequent surgery). Regarding the 9 patients with metastatic disease (among which 6 bone sarcomas), 6 had stable disease, 3 for more than 6 months (2 chondrosarcomas) and 3 for 3 to 6 months (1 dedifferentiated chondrosarcoma). Median progression-free survival and overall survival have been 4.5 and 13.9 months, respectively. Grade 3?C4 toxicity has only been hematologic without any symptoms.

Conclusion

In spite of a low response rate (14%), stable disease has often been observed in metastatic sarcomas. This proves that this combination has a real antitumoural activity, including against chemoresistant tumours such as the chondrosarcomas.     

Second-line,low-dose,weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line chemotherapy with carboplatin plus paclitaxel

BACKGROUND: Second-line chemotherapy with docetaxel improves survival and quality of life (QoL) in patients with nonsmall cell lung carcinoma (NSCLC) who fail first-line platinum-based regimens. The authors sought to determine the activity of second-line, low-dose, weekly paclitaxel in patients with NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. METHODS: Patients with Stage IIIB/IV NSCLC who had received first-line carboplatin/paclitaxel were treated with low-dose (80 mg/m(2)), weekly paclitaxel at the time of disease progression. Response rates, QoL, and survival were outcome end points. RESULTS: Sixty-two patients were included in this analysis. The median age was 62 years (range, 32-76 years), 55% of patients were male, 89% of patients had Stage IV NSCLC, and the Karnofsky performance status was 90-100% in 31% of patients, 70-80% in 55% of patients, and 60% in 14% of patients. Twenty-six percent of patients experienced disease progression as their best response to first-line carboplatin plus paclitaxel, whereas 52% of patients had stable disease, and 23% of patients had achieved a response. The median time from first-line carboplatin plus paclitaxel to second-line, low-dose, weekly paclitaxel was 9.5 weeks (range, 1-78 weeks). The toxicity profile was extremely favorable, with no Grade 4 toxicity and < 10% Grade 3 hematologic or nonhematologic toxicity in all patients with the exception of neuropathy. Ten percent of patients experienced both Grade 2 and Grade 3 neuropathy. The overall objective response rate was 8%. The median survival was 5.2 months (95% confidence interval [95%CI], 3.6-6.2 months), and the 1-year and 2-year survival rates were 20% (95%CI, 10-30%) and 9% (95%CI, 1-16%), respectively. CONCLUSIONS: Second-line, low-dose, weekly paclitaxel had activity in selected patients with Stage IIIB/IV NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. The toxicity profile of this approach is extremely favorable, and outcome expectations are similar to the outcome expectations with other single agents in this setting.     

High‐risk extracranial chondrosarcoma

BACKGROUND:

A study was undertaken to evaluate results of surgery and radiotherapy (RT) for high‐risk extracranial chondrosarcomas.

METHODS:

Between 1986 and 2006, 60 patients underwent surgery and RT for extracranial high‐risk chondrosarcoma. Preoperative RT (median, 50 gray [Gy]) and postoperative RT (median, 60 Gy) were used in 40% and 60% patients, respectively. Sites included pelvis/lower extremity (48%), chest wall (22%), spine/paraspinal (17%), and head and neck (13%). Overall, median tumor size was 7 cm (range, 1‐22 cm), and tumor grade was I, II, and III in 22%, 64%, and 14% of cases, respectively.

RESULTS:

Pathologically clear surgical margins (R0) were present in 50%, microscopic positive margins (R1) in 28%, and gross positive margins (R2) in 13%, half of whom had clinically detectable residual disease; surgical margin was unknown in 8%. Median follow‐up was 75 months (range, 5‐230 months). The crude local control rate was 90%. Patients with R0, R1, and R2 resections had local control of 100%, 94%, and 42%, respectively. Of the 8 cases that had R2 resection, 3 experienced uncontrolled progression, but 5 patients had stable disease with long‐term follow‐up. The 10‐year overall survival, progression‐free survival, and cause‐specific survival were 86%, 80.5%, and 89.4%, respectively. Younger age and grade III tumors were associated with worse progression‐free survival (P = .03 and .0003, respectively).

CONCLUSIONS:

Although surgery with complete resection is paramount in management of chondrosarcoma, RT is a useful adjuvant treatment and appears to offer excellent and durable local control where wide surgical resection is difficult to accomplish. Cancer 2011. © 2011 American Cancer Society.     

Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer

PURPOSE: The aim of our study was to assess prognostic factors and overall survival after salvage radiotherapy for patients who had endometrial carcinoma and who experienced an isolated vaginal recurrence. METHODS AND MATERIALS: We reviewed the records of 50 patients treated at our institution between 1967 and 2003 for an isolated vaginal recurrence of endometrial carcinoma. Initial treatment for endometrial carcinoma was definitive surgery in 49 patients and definitive radiotherapy in 1 patient. The median time from initial diagnosis of endometrial carcinoma to recurrence was 25 months (range, 4-179 months). Three patients (6%) received external-beam radiotherapy alone, 8 patients (16%) received brachytherapy only, and 39 patients (78%) received combined external-beam radiation therapy and brachytherapy. Median dose of radiation to the recurrence was 60 Gy (range, 16-85 Gy). Overall survival was calculated by the Kaplan-Meier method. Endpoints were measured from the date of diagnosis of the vaginal recurrence. Median follow-up of survivors after recurrence was 53 months (range, 8-159 months). RESULTS: The 5-year and 10-year disease-free and overall survivals were 68% and 55%, and 53% and 40%, respectively. On multivariate analysis, age (p = 0.0242), Grade 1 or 2 vs. Grade 3 tumor (p = 0.002), and size of recurrence (p < 0.001) were significant predictors of overall survival. All patients who had Grade 3 disease were dead by 3.6 years from the time of recurrence. Five patients experienced a Grade 3 or 4 complication. CONCLUSIONS: Patients treated with radiotherapy for an isolated vaginal recurrence can be cured in over 50% the cases. Radiotherapy is well tolerated, with a low risk of complications. Factors predictive of overall survival include tumor grade, patient age at recurrence, and tumor size.     

Central nervous system mesenchymal chondrosarcoma

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.     

Results of carbon ion radiotherapy in 152 patients

PURPOSE: This study summarizes the experience with raster scanned carbon ion radiation therapy (RT) at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, Germany since 1997. METHODS AND MATERIALS: Between December 1997 and December 2002, 152 patients were treated at GSI with carbon ion RT. Eighty-seven patients with chordomas and low-grade chondrosarcomas of the skull base received carbon ion RT alone (median dose 60 GyE); 21 patients with unfavorable adenoid cystic carcinomas and 17 patients with spinal (n = 9) and sacrococcygeal (n = 8) chordomas and chondrosarcomas were treated with combined photon and carbon ion RT. Twelve patients received reirradiation with carbon ions with or without photon RT for recurrent tumors. Furthermore, 15 patients with skull base tumors other than chordoma and low-grade chondrosarcoma were treated with carbon ions. RESULTS: Actuarial 3-year local control was 81% for chordomas, 100% for chondrosarcomas, and 62% for adenoid cystic carcinomas. Local control was obtained in 15/17 patients with spinal (8/9) and sacral (7/8) chordomas or chondrosarcomas and in 11/15 patients with skull base tumors other than chordomas and low-grade chondrosarcomas, respectively. Six of 12 patients who received reirradiation are still alive without signs of tumor progression. Common Toxicity Criteria Grade 4 or Grade 5 toxicity was not observed. CONCLUSION: Carbon ion therapy is safe with respect to toxicity and offers high local control rates for skull base tumors such as chordomas, low-grade chondrosarcomas, and unfavorable adenoid cystic carcinomas.     

High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial

PURPOSE: We completed a Phase I/II clinical trial (Lineberger Comprehensive Cancer Center 9603), in which we treated 62 Stage IIIA/IIIB inoperable non-small-cell lung cancer (NSCLC) patients with two cycles of induction carboplatin/paclitaxel chemotherapy, followed by concurrent weekly carboplatin/paclitaxel with radiation doses escalated from 60 to 74 Gy. The median survival of 24 months, 3-year survival rate of 38%, and the high dose of radiation used justified a critical analysis of the technical and clinical components of this trial. METHODS AND MATERIALS: Between 1996 and 1999, 62 sequential patients with inoperable Stage IIIA/IIIB NSCLC were enrolled and treated with two cycles of induction carboplatin (area under the concentration curve = 6 using the Calvert equation) and paclitaxel (225 mg/m(2)), followed by an escalating radiation dose of 60-74 Gy with concurrent carboplatin weekly (area under the concentration curve = 2) and paclitaxel weekly (45 mg/m(2)). The goals of the trial were to determine whether 74 Gy of radiation could be safely delivered under these circumstances and whether patients could potentially benefit in terms of survival. The radiation treatment plans for all 62 patients were reviewed to determine the prechemotherapy and postchemotherapy tumor volume, as well as the dose-volume histograms of the normal lung and esophagus. RESULTS: Of the 62 patients who entered the trial, 48 completed the entire course of treatment. At last follow-up, 20 patients were alive (crude survival rate 32%). With a median follow-up of 43 months, the median survival was 24 months. The survival rate was 50% at 2 years and 38% at 3 years. Cox regression analysis showed that survival was best predicted by whether the patient had received radiotherapy (finished the trial), performance status, disease stage, and log postchemotherapy tumor volume. The 3-year survival rate for the 48 patients finishing the trial was 45%. Eight patients (13%) suffered locoregional relapse as the only site of failure. Only 1 patient had Grade 2 radiation pneumonitis. Five patients (8%) had Radiation Therapy Oncology Group Grade 3 or 4 esophagitis; 40 (65%) had a Grade 1 or 2 esophagitis. Esophageal toxicity could be predicted by the length of esophagus receiving 40 or 60 Gy. CONCLUSION: Radiation doses of 74 Gy, when given under the guidelines of the Lineberger Comprehensive Cancer Center 9603, appear to be safe and may possibly contribute to increased survival in patients with inoperable Stage IIIA/IIIB NSCLC.     

Proton therapy for skull-base chondrosarcoma,a single-institution outcomes study

Background

We sought to evaluate the effectiveness of definitive or adjuvant external-beam proton therapy on local control and survival in patients with skull-base chondrosarcoma.

Methods

We reviewed the medical records of 43 patients with a median age of 49 years (range, 23–80 years) treated with double-scattered 3D conformal proton therapy for skull-base chondrosarcomas between January 2007 and February 2016. Proton therapy-related toxicities were scored using CTCAE v4.0.

Results

The median radiotherapy dose was 73.8 Gy(RBE) (range, 64.5–74.4 Gy[RBE]). Thirty-six (84%) and 7 (16%) patients underwent surgical resection or biopsy alone. Tumor grade distribution included: grade 1, 19 (44%) patients; grade 2, 22 (51%); and grade 3, 2 (5%). Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following surgery. The median follow-up was 3.7 years (range, 0.7–10.1 years). There were no acute grade 3 toxicities related to RT. At 4 years following RT, actuarial rates of overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were 95%, 100%, 89%, and 95%.

Conclusion

High-dose, double-scattered 3D conformal proton therapy alone or following surgical resection for skull-base chondrosarcoma is an effective treatment with a high rate of local control with no acute grade 3 radiation-related toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

     

Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2); final report of RTOG 89-01. Radiation Therapy Oncology Group

PURPOSE: To compare the outcome of treatment of mediastinoscopy-verified N2 non-small-cell lung cancer treated with induction chemotherapy followed by either surgery or radiotherapy (RT), with both options followed by consolidation chemotherapy. METHODS AND MATERIALS: A randomized Phase III trial for Stage IIIA (T1-T3N2M0) non-small cell lung cancer was conducted by the Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group between April 1990 and April 1994. After documentation of N2 disease by mediastinoscopy or anterior mediastinotomy, patients received induction chemotherapy with cisplatin, vinblastine, and mitomycin-C. Mitomycin-C was later dropped from the induction regimen. Patients were then randomized to surgery or RT (64 Gy in 7 weeks) followed by cisplatin and vinblastine. RESULTS: RTOG 89-01 accrued 75 patients, of whom 73 were eligible and analyzable. Twelve patients received induction chemotherapy but were not randomized to RT or surgery thereafter. Forty-five patients were randomized to postinduction RT or surgery. Of the analyzable patients, 90% had a Karnofsky performance score of 90-100, 18% had weight loss >5%, 37% had squamous cell histologic features, and 54% had bulky N2 disease. The distribution of bulky N2 disease was uniform among the treatment arms. The incidence of Grade 4 toxicity was 56% in patients receiving mitomycin-C and 29% in those who did not. Only 1 patient in each group had acute nonhematologic toxicity greater than Grade 3 (nausea and vomiting). No acute Grade 4 radiation toxicity developed. The incidences of long-term toxicity were equivalent across the arms. Three treatment-related deaths occurred: 2 patients in the surgical arms (one late pulmonary toxicity and one pulmonary embolus), and 1 patient in the radiation arm (radiation pneumonitis). Induction chemotherapy was completed in 78% of the patients. Complete resection was performed in 73% of 26 patients undergoing thoracotomy. Consolidation chemotherapy was completed in 75% of the patients. No statistically significant difference was found among the treatment arms. The overall progression-free survival rate was 53% at 1 year and 17% at 3 years. The median progression-free survival was 14 months. No difference in the 1-year survival rate (70% vs. 66%) or median survival time (19.4 vs. 17.4 months) between the surgery and RT arms. The median survival in the patients receiving induction chemotherapy only was 8.9 months. Mitomycin-C had no impact on survival (p = 0.75). No statistically significant difference was noted in the time to local failure between the surgical and RT arms. CONCLUSION: The patient accrual to this trial made its results inconclusive, but several observations are notable. In this trial, histologic confirmation of N2 disease in the surgical and nonsurgical arms eliminated the usual biases from clinical staging. In this setting, local control and survival were essentially equal between the surgical and RT arms. The 3- and 5-year survival rates of nonsurgical therapy were comparable to published surgical trials of N2 disease.