Chordoma and chondrosarcoma: similar, but quite different, skull base tumors

BACKGROUND: Chordoma and chondrosarcoma of the skull base are frequently amalgamated because of similar anatomic location, clinical presentation, and radiologic findings. The chondroid chordoma variant has been reported to carry a better prognosis. The objective of the current study was to investigate the distinctions between these 3 entities. METHODS: The data concerning 109 patients with chordoma, chondroid chordoma, and chondrosarcoma who were treated by a single surgeon with maximum surgical resection and frequently by adjunct proton beam radiotherapy between 1990 and 2006 were analyzed retrospectively. Pathologic distinction was established by cytokeratin and epithelial membrane antigen staining. Clinical, radiologic, pathologic, and cytogenetic studies were analyzed in relation to disease recurrence and death. RESULTS: The average follow-up was 48+/-37.5 months (range, 1-191 months). There were no reliable distinguishing clinical or radiologic features noted between the groups. Chondrosarcoma patients had a significantly better outcome compared with chordoma patients with regard to survival and recurrence-free survival (P=.028 and P<.001, respectively), whereas patients with chondroid chordoma had a poor outcome similar to chordoma patients with regard to survival and recurrence-free survival (P=.337 and P=.906, respectively). CONCLUSIONS: Chordoma and chondrosarcoma differ with regard to their origin and histology, and differ markedly with regard to outcome. Chondroid chordomas behave in a manner that is clinically similar to chordomas, with the same prognosis. Both chordoma types demonstrate an aggressive clinical course and poor outcome after disease recurrence. The optimal treatment for all groups of patients involves radical surgical resection followed by high-dose radiotherapy in patients with chordomas. Radiotherapy may not be necessary in patients with low-grade chondrosarcoma.     

质子碳离子笔形束扫描技术治疗头颈部脊索瘤与软骨肉瘤的初步结果

目的 采用质子碳离子笔形束扫描技术治疗头颈部脊索瘤软骨肉瘤患者的不良反应和近期疗效。方法 2014-2016年共收治61例接受质子重离子治疗作为首程放疗的头颈部脊索瘤及软骨肉瘤患者,其中脊索瘤45例,软骨肉瘤16例;男39例,女22例;中位年龄38岁(14~70岁),中位肿瘤最大直径4.1 cm (0~8.6 cm)。肿瘤原发部位以枕骨斜坡及颈椎为主。结果 单纯质子治疗8例,质子+碳离子治疗21例,单纯碳离子治疗32例,所有患者均顺利完成治疗。患者中位随访时间21个月(7~47个月)。未见3-4级急性不良反应,晚期不良反应仅1例放射性颞叶损伤。2年无进展生存率91%,2年总生存率100%。结论 质子重离子治疗脊索瘤软骨肉瘤取得了较好的短期疗效,长期疗效及不良反应仍需要进一步随访。     

Central nervous system involvement in children with sarcoma

OBJECTIVES: To summarize and analyze the experience in CNS involvement (CNSI) in children with sarcomas treated in the above-mentioned institutions. PATIENTS AND METHODS: From 1990 to 2001, all medical charts were retrospectively reviewed: 19 sarcoma patients (12 boys and 7 girls) were diagnosed with CNSI (4 osteogenic sarcomas, 11 Ewing sarcomas, 2 rhabdomyosarcomas, 1 alveolar soft part sarcoma and 1 mesenchymal chondrosarcoma). Mean age of all patients at the time of initial diagnosis was 14.9 years (range: 4-24 years), mean age at the time when CNSI was diagnosed was 16.9 years (range: 5.5-27 years). RESULTS: The frequency of CNSI among our patients was 6.17%. The following symptoms and signs (sometimes combined) presented: headache (10 patients), nausea and vomiting (6 patients), seizures (11 patients) and focal neurological signs (9 patients). The mean duration of time elapsed since diagnosis of CNSI till death or last follow-up was 5.2 months (SD: +/-5.7 months). Four patients received chemotherapy (CT) alone, 8 CT and radiotherapy (RT), 2 RT alone, 3 supportive treatment only, 1 CT and surgery and 1 surgery alone. Sixteen patients died; there was no significant difference in the duration of survival between those who were treated with RT or surgery (mean +/- SD: 6.77 +/- 6.56 months) and those who received only CT or supportive treatment (mean +/- SD: 2.60 +/- 2.94 months) (p = 0.07). Brain disease was the main cause of death in all but 1 patient who died 4 days after autologous bone marrow transplantation from uncontrolled sepsis. In 16 patients, CNSI was part of a metastatic disease. CONCLUSIONS: Among children with sarcoma, CNSI is encountered in 6.17% of cases. More effective therapy has to be developed in order to improve their outcome.     

Objective and noninvasive detection of sub-clinical lung injury in breast cancer patients after radiotherapy.

AIMS: We employed technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) lung scan to detect sub-clinical lung injury after radiation therapy of 60 female patients diagnosed with right breast cancer. METHODS: The degree of pulmonary vascular endothelium damage was represented as lung/liver uptake ratios (L/L ratios) calculated on Tc-99m HMPAO lung scan. All patients underwent simple mastectomy and post-operative radiotherapy of approximately 50 Gy. We divided the patients into three groups according to the interval between radiotherapy and lung Tc-99m HMPAO lung scan: Group 1 included 20 patients who received the lung scan within 1-3 months after radiotherapy, group 2 included 20 patients were within 3-9 months after radiotherapy, and group 3 included 20 patients were more than 9 months after radiotherapy. In addition, 20 age-matched normal women were included as the control group. RESULTS: The L/L ratios were 0.32+/-0.04 for normal controls, 0.59+/-0.10 for group 1, 0.55+/-0.07 for group 2, and 0.34+/-0.04 for group 3, respectively. Based on our preliminary results, we found that sub-clinical lung injury and significantly increased L/L ratio in breast cancer patients received radiotherapy may occur within the first 6 months after radiotherapy. However, the L/L ratio is markedly decreased after 9 months. CONCLUSION: Our findings concluded that the degree of pulmonary vascular endothelium damage represented as the L/L ratio on Tc-99m HMPAO lung scan has the potential to be a sensitive, objective and noninvasive method to detect sub-clinical lung injury in breast cancer patients received radiotherapy.     

Chondrosarcoma of the scapula: long-term oncologic outcome

BACKGROUND: Chondrosarcoma is the second most common primary sarcoma of bone. It often develops within flat bones, such as the pelvis, ribs, and scapula. In the current study, the authors reviewed the surgical experience and long-term oncologic outcomes of patients with chondrosarcoma arising in the scapula. METHODS: The medical records of 29 consecutive patients with chondrosarcoma of the scapula were reviewed. The patients were treated between 1954 and 1994. All patients had localized disease at the time of presentation. The tumors were classified histologically as Grade 1 (10 patients), Grade 2 (10 patients), Grade 3 (7 patients), dedifferentiated (1 patient), and mesenchymal (1 patient) (using the criteria of Evans et al.). The mean maximal dimension of the tumors was 11 cm. Twenty-five patients underwent limb-sparing surgical resection and 4 patients underwent forequarter amputations. The median follow-up was 13 years (range, 1-35 years). RESULTS: At last follow-up, 22 patients (76%) were free of disease and 7 patients (24%) had died of their disease. Local recurrence occurred in 4 patients at 7 months, 16 months, 40 months, and 43 months, respectively. The local recurrence-free survival rate was 86% at 5 years, 10 years, and 20 years. Disease-specific survival was 83% at 5 years, 74% at 10 years, and 74% at 20 years. Patients who had low-grade chondrosarcomas had better survival compared with patients who had high-grade chondrosarcomas (P = 0.07). CONCLUSIONS: Patients who had localized chondrosarcoma of the scapula had a favorable long-term outcome, most likely due to the unique anatomic features that improved the likelihood of achieving wide surgical margins with limb-sparing surgery, despite the frequent presentation of locally advanced disease.     

Gamma knife radiosurgery of imaging-diagnosed intracranial meningioma

PURPOSE: To evaluate tumor control and outcome from radiosurgery of meningiomas diagnosed by imaging without pathologic verification. METHODS AND MATERIALS: A total of 219 meningiomas diagnosed by imaging criteria underwent gamma knife radiosurgery to a median marginal tumor dose of 14 Gy (range 8.9-20), a median treatment volume of 5.0 cm(3) (range 0.47-56.5), and a median maximal dose of 28 Gy (range 22-50). The median follow-up was 29 months (range 2-164). RESULTS: Tumor progression developed in 7 cases, 2 of which turned out to be different tumors (metastatic nasopharyngeal adenoid cystic carcinoma and chondrosarcoma). One tumor was controlled, but the development of other brain metastases suggested a different diagnosis. The actuarial tumor control rate was 93.2% +/- 2.7% at 5 and 10 years. The actuarial rate of identifying a diagnosis other than meningioma was 2.3% +/- 1.4% at 5 and 10 years. The actuarial rate of developing any postradiosurgical injury reaction was 8.8% +/- 3.0% at 5 and 10 years. No pretreatment variables correlated with tumor control in univariate or multivariate analysis. The risk of postradiosurgery sequelae was lower (5.3% +/- 2.3%) in patients treated after 1991 (with stereotactic MRI and lower doses; p = 0.0104) and tended to increase with treatment volume (p = 0.0537). CONCLUSION: Radiosurgery of meningioma diagnosed by imaging without tissue confirmation is associated with a high rate of tumor control and acceptable morbidity but carries a small risk (2.3%) of an incorrect diagnosis.     

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.     

Is it necessary to treat all patients with idiopathic pulmonary fibrosis?

BACKGROUND AND AIM OF THE WORK: To investigate the clinical course of untreated patients with idiopathic pulmonary fibrosis (usual interstitial pneumonia) (IPF/UIP). METHODS: Forty-three patients with IPF/UIP, divided into two groups. Group I consisted of 29 patients treated at diagnosis, while Group II comprised 14 patients who did not receive treatment. The indication of treatment was established whenever patients referred to a significant progression of the degree of dyspnea during the year prior to diagnosis. RESULTS: At diagnosis, patients from Group I had lower FVC (mean +/- SEM, 56+/-3% vs 73+/-3%) (p = 0.0004) and a greater extent of ground glass pattern in high resolution CT scan (18+/-4% vs 4+/-1%) (p = 0.004) than those from Group II. In group I, a follow-up study was carried out on 26 patients for 24+/-4 months. Thirteen of these 26 patients (50%) died 11+/-4 months after the initial assessment. Serial pulmonary functional tests were performed on 19 patients. Thirteen patients from Group II were followed up for 23+/-3 months. Seven of these 13 patients were treated 12+/-3 months after the diagnosis because of progression of the disease. The remaining 6 patients remained untreated and with the disease stable at the end of the follow-up, representing 15% (6 out of 39) of the whole study group. No patients from this group died during the follow-up. At the end of the follow-up, there were no differences in lung function changes between treated patients (19 from Group I and 7 from Group II), and the 6 untreated patients. CONCLUSIONS: Some patients with IPF/UIP remain stable for extended periods of time without treatment.     

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.     

Soft tissue sarcomas of the popliteal fossa: outcome and risk factors.

BACKGROUND: Limb salvage surgery of popliteal soft tissue sarcomas may be hampered due to the incomplete anatomical containment of this region and the vicinity of neurovascular structures. The scope of this study was to determine outcome and to define risk factors. PATIENTS AND METHODS: 27 patients (53.3+/-15.8 y; 16/27 male) with popliteal soft tissue sarcomas were assessed. Mean follow-up was 40.9+/-33.8 months (48.5+/-36.7 months in surviving patients). 9/27 patients were included after prior treatment elsewhere (5 after intralesional resections and 4 local recurrences). The lesions were staged IB in 8/27 patients, IIB in 17/27 and III in 2/27. Immediate amputations were performed in 7/27 patients. 15/27 patients were subjected to radiation therapy (preoperative in 6/15 cases), 8/27 patients received chemotherapy (5/8 preoperatively). RESULTS: Overall survival and disease-free survival at 5 y was 63.0% and 59.5%. Local recurrence occurred in 2 patients. 8/27 patients developed metastatic disease after 28.9+/-9.8 months. Survival (p=0.397) and disease-free survival (p=0.113) did not differ in patients after amputations vs limb salvage. Application of radiation therapy was associated with a better survival (p=0.003). Complications related to the surgical intervention were recorded in 2/27 patients, complications related to radiation therapy occurred in 6/15 patients. DISCUSSION: Despite being extra-compartmental, popliteal sarcomas can be treated with a high rate of limb salvage while equal safety compared to amputations is maintained. Irradiation improved survival in our patient population. In cases with involvement of neurovascular structures, preoperative down-staging with radio or chemo-therapy may prevent amputation.     

骨盆软骨肉瘤的手术治疗

目的总结骨盆软骨肉瘤的手术切除、重建、并发症和疗效。方法回顾性分析手术治疗的21例骨盆软骨肉瘤患者的临床资料。其中男性9例,女性12例;年龄16~65岁,中位年龄46岁。根据Ennek ing骨盆肿瘤分区：Ⅰ区2例,Ⅰ和Ⅱ区5例,Ⅱ区6例,Ⅱ和Ⅲ区7例,Ⅲ区1例。高分化软骨肉瘤12例,中分化软骨肉瘤5例,低分化软骨肉瘤2例,间叶性软骨肉瘤2例。肿瘤刮除灭活＋异体骨植骨2例;髂骨翼大块切除＋钉棒系统重建1例;髂骨大块切除＋异体肱骨螺钉重建1例;耻骨切除自体髂骨移植钢板螺钉重建1例;半骨盆截肢2例;内半盆切除5例;围髋臼切除重建9例。结果21例患者随访时间7-100月,平均39月。17例患者无瘤生存,2例带瘤生存,2例死亡。16例行广泛切除术中5例局部复发,5例行边缘性和经病灶切除术中3例局部复发。软骨肉瘤的复发率为38.1%,死亡率为9.5%。19例生存患者参加功能评价,根据国际保肢学会功能评分系统,总分7~25分,平均19分。8例患者术后出现可控性并发症。结论骨盆软骨肉瘤治疗首选广泛性切除,积极预防和处理并发症是保证手术成功的关键。     

Image-guided,intensity-modulated radiation therapy (IG-IMRT) for skull base chordoma and chondrosarcoma: preliminary outcomes

Background

We report our preliminary outcomes following high-dose image-guided intensity modulated radiotherapy (IG-IMRT) for skull base chordoma and chondrosarcoma.

Methods

Forty-two consecutive IG-IMRT patients, with either skull base chordoma (n = 24) or chondrosarcoma (n = 18) treated between August 2001 and December 2012 were reviewed. The median follow-up was 36 months (range, 3–90 mo) in the chordoma cohort, and 67 months (range, 15–125) in the chondrosarcoma cohort. Initial surgery included biopsy (7% of patients), subtotal resection (57% of patients), and gross total resection (36% of patients). The median IG-IMRT total doses in the chondrosarcoma and chordoma cohorts were 70 Gy and 76 Gy, respectively, delivered with 2 Gy/fraction.

Results

For the chordoma and chondrosarcoma cohorts, the 5-year overall survival and local control rates were 85.6% and 65.3%, and 87.8% and 88.1%, respectively. In total, 10 patients progressed locally: 8 were chordoma patients and 2 chondrosarcoma patients. Both chondrosarcoma failures were in higher-grade tumors (grades 2 and 3). None of the 8 patients with grade 1 chondrosarcoma failed, with a median follow-up of 77 months (range, 34–125). There were 8 radiation-induced late effects—the most significant was a radiation-induced secondary malignancy occurring 6.7 years following IG-IMRT. Gross total resection and age were predictors of local control in the chordoma and chondrosarcoma patients, respectively.

Conclusions

We report favorable survival, local control and adverse event rates following high dose IG-IMRT. Further follow-up is needed to confirm long-term efficacy.     

External irradiation of growth hormone producing pituitary adenomas: prolactin as a marker of hypothalamic and pituitary effects

Fifty-six patients with acromegaly were treated with external irradiation, 50 Gy, after unsuccessful pituitary surgery. A 50% reduction of pre-irradiation growth hormone levels was obtained in 51/56 patients. This level was reached after 26 +/- 14 months in 33 patients with prolactin levels less than 25 micrograms/l at diagnosis, after 21 +/- 17 months in 18 patients with prolactin greater than or equal to 25 micrograms/l, and after 20 +/- 21 months in 12 patients with prolactin greater than 40 micrograms/l at diagnosis. A further 50% decrease of growth hormone levels was obtained in 40/51 patients 42 +/- 22 months after radiotherapy, indicating that in clearly responsive patients, the growth hormone depression after radiotherapy follows a first order reaction. Four patients did not reach a 50% reduction of growth hormone levels 48-80 months after radiotherapy. During 10 years of follow-up, the growth hormone depression tended to be more pronounced in patients with mixed secretion of growth hormone and prolactin. The reduction of growth hormone levels was not correlated with the irradiated volume or the cumulative radiation effect. Within the first year, prolactin increased within the normal range in normoprolactinemic patients and remained so during follow-up. In hyperprolactinemic patients, prolactin decreased successively but to a lesser extent than growth hormone. Pituitary insufficiencies increased over time and three patients developed GH-insufficiency. Hypothalamic damage as indicated by prolactin changes was a regular phenomenon after radiotherapy.     

The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence

BACKGROUND: The prognostic significance of isolated tumor cells (ITCs) in bone marrow (BM) from patients with breast carcinoma at the time of their primary diagnosis recently was been confirmed by a large pooled analysis. If the persistence of ITCs after adjuvant therapy confers a similar risk for recurrence, then it would be an indication to consider secondary adjuvant therapy. METHODS: The authors analyzed BM aspirates from 228 patients during recurrence-free follow-up at a median interval +/- standard deviation (SD) of 21.3 +/- 29.1 months after a primary diagnosis of breast carcinoma (pathologic T1 [pT1]-pT2, pN0-pN3, pM0). Carcinoma cells were detected using a standardized immunoassay with monoclonal antibody A45-B/B3 directed against cytokeratin (CK). Patients were followed for a median +/- SD of 49.8 +/- 32.1 months after their primary diagnosis. RESULTS: Persistent ITCs in BM were detected in 12.7% of patients (n=29 patients). Positive BM status was more frequent (15.7%) within the first 21 months after primary diagnosis than after a follow-up > 21 months (9.7%). The Kaplan-Meier estimate for mean recurrence-free survival was 149.7 months (95% confidence interval [95% CI], 139.6-159.8 months) in patients with negative BM status and 86.5 months (95% CI, 65.7-107.4 months; P=0.0003) in patients with positive BM status at the time patients underwent follow-up BM aspiration. Patients who were without evidence of persistent ITCs had a significantly longer overall survival (162.1 months; 95% CI, 152.1-172.0 months) compared with patients who had positive BM status (overall survival, 98.7 months; 95% CI, 79.7-117.9 months; P=0.0008). In multivariate Cox regression analysis that included BM status, tumor size, lymph node status, and histopathologic grade, evidence of ITCs was an independent significant predictor for reduced disease-free survival (relative risk [RR], 4.57; P <0.0001) and overall survival (RR, 5.57; P=0.002). Persistent ITCs had the greatest prognostic relevance when they were detected between 25 months and 42 months after primary diagnosis (RR, 7.68). CONCLUSIONS: Evidence of persistent ITCs in BM from patients with breast carcinoma indicated an increased risk for subsequent recurrence. Prospective trials should investigate the benefit of secondary adjuvant treatment on the basis of BM marrow status.     

The dosimetry of prostate brachytherapy-induced urethral strictures

PURPOSE: There is a paucity of data regarding the incidence of urethral strictures after prostate brachytherapy. In this study, we evaluate multiple clinical, treatment, and dosimetric parameters to identify factors associated with the development of brachytherapy-induced urethral strictures. METHODS AND MATERIALS: 425 patients underwent transperineal ultrasound-guided prostate brachytherapy using either (103)Pd or (125)I for clinical T1b/T3a NxM0 (1997, American Joint Committee on Cancer) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. 221 patients were implanted with (103)Pd and 204 patients with (125)I. The median patient age was 68 years (range 48-81 years). The median follow-up was 35.2 months (range 15-72 months). Follow-up was calculated from the day of implantation. Thirteen patients developed brachytherapy-induced strictures, and all strictures involved the membranous urethra. A control group of 35 patients was rigorously matched to the stricture patients in terms of treatment approach; i.e., choice of isotope, plus or minus radiation therapy, and plus or minus hormonal manipulation. Nine of the 13 stricture patients had detailed Day 0 urethral dosimetry available for review. The apex of the prostate gland and the membranous urethra were defined by CT evaluation. Urethral dosimetry was reported for the prostatic urethra, the apical slice of the prostate gland, and the membranous urethra which was defined as extending 20 mm in length. RESULTS: The 5-year actuarial risk of a urethral stricture was 5.3%, with a median time to development of 26.6 months (range 7.8-44.1 months). Of multiple clinical and treatment parameters evaluated, only the duration of hormonal manipulation (>4 months, p = 0.011) was predictive for the development of a urethral stricture. The radiation dose to the membranous urethra was significantly greater in patients with strictures than those without: 97.6% +/- 20.8% vs. 81.0% +/- 19.8% of prescribed minimum prostate dose, mPD (p = 0.031). The urethral dose 20 mm distal to the prostate apex was 57.6% +/- 23.8% vs. 31.5% +/- 13.9% of mPD for the stricture and control patients, respectively (p = 0.011). In addition, the extent of the 75% mPD and 50% mPD levels beyond the prostatic apex was also significantly greater for stricture patients, 16.6 +/- 5.3 mm vs. 11.9 +/- 4.5 mm (p = 0.010) and 19.0 +/- 3.2 mm vs. 16.0 +/- 3.4 mm (p = 0.021), respectively. Dose to the prostatic urethra was not predictive of stricture, but the magnitude and extent of high-dose regions within the prostate were predictive of stricture. Twelve of the 13 patients who developed urethral strictures were successfully managed by dilatation/transurethral incision. To date, 1 of the 12 patients has required a second dilatation. The remaining patient developed an iatrogenic induced injury and was catheter-dependent for 6 months. CONCLUSIONS: After prostate brachytherapy, the actuarial 5-year incidence of urethral strictures is 5.3% with a median time to development of 26.6 months. All strictures involved the membranous urethra and occurred within the first 44 months after brachytherapy. In most cases, membranous urethral strictures are easily managed with dilatation/incision. Factors predicting for the development of a urethral stricture included the magnitude and extent of high-dose regions within the prostate, the mean membranous urethra dose and the dose 20 mm distal to the prostatic apex, the maximum extent along the membranous urethra of certain dose levels, and the duration of hormonal manipulation.     

Diagnosis and treatment of mesenchymal chondrosarcoma

Eight cases of mesenchymal chondrosarcoma (3 males and 5 females aged 15-65) are described. Morphological examination revealed in all cases biphasal tumor consisting of the chondroid tissue of varying maturity and undifferentiated tissue. Combination and complex treatment was given to 6 patients. In 4 cases, radiotherapy was carried out in combination with chemotherapy and local electromagnetic hyperthermia. Out of 8 patients, seven are still alive and are examined at 4 month - 11 year intervals (average of 39.7 months). One female patient died 12 months after the beginning of treatment. Combined and complex procedures should be recommended for treatment of such patients.     

GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/US and French National Cancer Institute Single-Arm Phase II Collaborative Study

BackgroundPre-clinical data have suggested a therapeutic role of Hedgehog (Hh) pathway inhibitors in chondrosarcoma.MethodsThis phase II trial included patients with progressive advanced chondrosarcoma. They received GDC-0449 150 mg/day (days 1–28, 28-day cycle). The primary end point was the 6-month clinical benefit rate (CBR) defined as the proportion of patients with non-progressive disease at 6 months. A 6-month CBR of 40% was considered as a reasonable objective to claim drug efficacy.ResultsBetween February 2011 and February 2012, 45 patients were included. Twenty had received prior chemotherapy. Thirty-nine were assessable for efficacy. The 6-month CBR was 25.6% (95% confidence interval 13.0–42.1). All stable patients had grade 1 or 2 conventional chondrosarcoma with documented progression within the 6 months before inclusion. All but one with available data also had overexpression of the Hh ligand. Median progression-free and overall survivals were 3.5 and 12.4 months, respectively. The most frequent adverse events were grade 1 or 2 myalgia, dysgeusia and alopecia.ConclusionsGDC-0449 did not meet the primary end point of this trial. Results suggest some activity in a subset of patients with progressive grade 1 or 2 conventional chondrosarcoma. Further studies assessing its role in combination with chemotherapy are warranted.ClinicalTrials.gov IdentifierNCT01267955.     

Craniofacial osseous and chondromatous sarcomas in British Columbia--a review of 34 cases

Head and neck sarcomas are very rare diseases. The aim of this study was to assess the prevalence and presentation of hard tissue sarcomas in the head and neck and jaws. A search of the British Columbia Tumor Registry identified 34 craniofacial hard tissue sarcomas (11 chondrosarcomas, 23 osteosarcomas) over a period of 29 years. A male predominance (1.8:1) and a mean age of 40.4 years at diagnosis were seen. Of the 23 patients with osteosarcoma, one-third survived for 5 years and 12 (52%) died within a mean of 20 months. Of the 11 patients with chondrosarcoma, 45% survived for 5 years and two (18%) of the patients died within a mean of 6 months. In nine of the osteosarcoma patients (39%) the jaws were involved, and in six of those cases (67%) there was mandibular involvement. Swelling was the first sign in all jaw patients, with a mean age of 41.1 years at diagnosis and a male predominance with a ratio of 8:1. Three of the eight male patients with osteosarcoma of the jaw (38%) died within a mean of less than 1 year. Improved prognosis is related to early recognition and diagnosis to allow for adequate surgical resection. The benefit of a combination of surgery with irradiation or chemotherapy continues to be investigated.