The role of radiation therapy in the management of head and neck paragangliomas: impact of quality of life versus treatment response.

PURPOSE: To assess the impact of radiotherapy in paragangliomas (PGLs) with regard to overall survival, local control, volumetric response and particularly quality of life (QoL). MATERIALS AND METHODS: From 1985 to 2010, 130 cases of head and neck (H&N) PGLs were managed at Bordeaux University Hospital. With a median follow-up of 7.6 years, we retrospectively present a cohort of 30 consecutive patients treated with radiation therapy for H&N PGLs. QoL was evaluated for 20 patients by the EORTC QLQ-C30 and H&N35 questionnaires through a cross-sectional study. RESULTS: The 5-year overall survival and local control were 95% and 96% respectively. QoL is altered following management of PGLs. The H&N35 score is lower after combined modality therapy (surgery±embolization and radiation therapy) for speech and hearing (p=0.004), trismus (p=0.003) and total score (p=0.01) than after radiotherapy alone. Tumor shrinkage was significant at 2 and 3 years after radiotherapy (p=0.018; p=0.043). CONCLUSION: Ultimate QoL should be a major goal of any treatment strategy for this benign disease. Definitive radiotherapy should be considered as a reasonable alternative to multimodality treatment as it provides comparable disease control with an apparent improvement in QoL.

Meningeal carcinomatosis of the internal auditory meatus: clinical and imagery-aided differentiation.

OBJECTIVES: To describe difficulties in diagnosing meningeal carcinomatosis of the internal auditory meatus (IAM-MC). STUDY DESIGN: Retrospective case review. SETTING: Tertiary skull base surgery referral center. PATIENTS: A series of six cases of patients diagnosed with IAM-CM over 14 years. RESULTS: The primary cancer was known before diagnosis in three cases (adenocarcinoma of lung, breast, and melanoma). In two others, it was discovered at workup (lung, ethmoid adenocarcinoma). In the last case, no primary cancer was identified. Vestibular symptoms were the first complaint in five of the six cases. Referral symptom was facial paralysis in five cases and rapid-onset total deafness associated with severe unsteadiness in one. Rapid hearing decrease and symptoms of bilateralization were observed in five cases. Diagnosis was ascertained by discovery of malignant cells in the CSF in three cases and at tumor biopsy in one case. In the two other cases, the association of brain metastases and increased dura mater infiltration was convincing. Treatment consisted in radiation therapy to the whole brain in five cases and intrathecal chemotherapy in one case. Evolution was rapidly lethal in five cases. The last died free of disease 4 years after treatment. CONCLUSION: IAM-MC is difficult to demonstrate. Progressive facial paralysis associated with aggressive and rapidly bilateral cochlear and vestibular symptoms are highly evocative in the event of cancer in the patient's history. If there is no history of cancer, lumbar puncture is to be repeated until malignant cells are discovered in the CSF before beginning radiotherapy.

Inflammatory myofibroblastic tumour of the skull base.

Inflammatory myofibroblastic tumors (IMTs) are rare benign clinical and pathological entities. IMTs have been described in the lungs, abdomen, retroperitoneum, and extremities but rarely in the head and neck region. A 38-year-old man presented with headache, right exophthalmia, and right 6th nerve palsy. A CT scan revealed enlargement of the right cavernous sinus and osteolytic lesions of the right sphenoid and clivus. MR imaging showed a large tumor of the skull base which was invading the sella turcica, right cavernous sinus, and sphenoidal sinus. A biopsy was performed and revealed an IMT. Corticosteroids were given for 3 months but were inefficient. In the framework of our pluridisciplinary consultation, fractionated conformal radiotherapy (FRT) was indicated at a low dose; 20 Gy in 10 fractions of 2 Gy over 12 days were delivered. Clinical response was complete 3 months after FRT. Radiological response was subtotal 6 months after FRT. Two years later, the patient is well.

Waiting times before initiation of radiotherapy might not affect outcomes for patients with glioblastoma: a French retrospective analysis of patients treated in the era of concomitant temozolomide and radiotherapy.

Purpose of this study was to determine the effect of waiting time for radiotherapy on overall survival of patients with glioblastoma treated in the EORTC-NCIC trial at 18 centers in France. A total of 400 adult patients with glioblastoma who were treated between January 1, 2006 and December 31, 2006 were included. There were 282 patients with "minimum criteria" according to the EORTC-NCIC trial: (i) concurrent chemotherapy with temozolomide; and (ii) age between 18 and 70 years old. Among these patients, 229 were treated with adjuvant temozolomide and were classified as "maximal criteria". One-hundred and eighteen patients were in the "without minimal criteria" group. Waiting time from the first symptom (FS-RT), pathology diagnosis (P-RT), multidisciplinary meeting (MM-RT), surgery (S-RT), and CT scan for delineation (CT-RT) until the start of radiotherapy were recorded. Median follow-up for all patients was 327 days. Overall, median FS-RT, P-RT, MM-RT, CT-RT, and S-RT times were 77, 36, 32, 12, and 41 days, respectively. Median, and 12 and 24-month overall survival were 409 days, and 56.3 ± 2.1 % and 27.6 ± 2.6 %, respectively. Univariate analysis failed to reveal a difference in survival, irrespective of the delay. In multivariate analysis, independent favorable prognostic factors for overall survival were age (p ≤ 0.0001) and type of surgery (p = 0.0006). In this large series treated during the EORTC-NCIC protocol period, waiting time until radiotherapy did not seem to affect patient outcome.

Unique case of malignant transformation of a vestibular schwannoma after fractionated radiotherapy.

OBJECTIVE: Malignant transformation of vestibular schwannoma is considered a rare clinical entity. Radiotherapy, as a treatment option for vestibular schwannoma, is regarded as a potential risk factor for secondary malignancy. Recently, radiotherapy with dose fractionation has been proposed, intended to diminish the risk of radiation-induced neuropathy. CASE PRESENTATION: The aim of the present study is to report the first case, to the best of our knowledge, of malignant transformation of a residual vestibular schwannoma 19 years after fractionated radiotherapy, describing its characteristics with regard to those previously reported in the literature. CONCLUSIONS: The main purpose of the present work is to state that the knowledge of the iatrogenic potential pitfalls of any technique of radiotherapy in clinical oncology is becoming a necessity. Finally, our report demonstrates that the irradiated patients must be monitored for life because a secondary malignancy may appear after a very long delay.

Salvage radiotherapy after high-intensity focussed ultrasound for recurrent localised prostate cancer.

BACKGROUND: Radiotherapy is a treatment option in the case of local failure following treatment for localised prostate cancer with high-intensity focussed ultrasound (HIFU). OBJECTIVE: Our aim was to evaluate tolerance and oncologic control with salvage radiotherapy (SRT) after HIFU failure and to identify predictive factors of success. DESIGN, SETTING, AND PARTICIPANTS: From March 1995 to March 2008, all patients who presented with histologically proven persistent local disease following HIFU and were treated with curative intent SRT (with or without hormonal treatment) were included in this single-centre retrospective study. INTERVENTION: Patients underwent conformal radiotherapy. The median dose of conformal treatment was 72 Gy (65-78 Gy). MEASUREMENTS: The primary outcome measure was progression-free survival (PFS) defined as no biochemical relapse (three consecutive rises in prostate-specific antigen [PSA] with a velocity >0.4 ng/ml per year or PSA >1.5 ng/ml) and no additional treatment. Predictive factors of failure were examined in univariate and multivariate analyses. Adverse events in terms of urinary and digestive toxicity, urine incontinence, and erectile dysfunction (ED) were reported. RESULTS AND LIMITATIONS: The median (range) and mean (standard deviation) follow-up of the 100 patients analysed was 33 mo (5-164 mo) and 37.2 mo (23.6 mo), respectively. Eighty-three patients received SRT alone, and 17 received SRT and androgen-deprivation therapy. For the 83 patients treated with exclusive radiation therapy, PFS was 72.5% at 5 yr and 93%, 67%, and 55% for the low-, intermediate-, and high-risk groups, respectively. In the univariate analysis, PSA level prior to SRT, risk status, PSA nadir after SRT, PSA nadir after SRT >0.2 ng/ml, and time to achieve this nadir were all predictive of failure. In the multivariate analysis, PSA nadir post-SRT with a threshold at 0.2 ng/ml and time to achieve this nadir were the significant predictive factors of failure. Gastrointestinal toxicity was low; urinary toxicity grade < or =2 was 34.5%. Four were grade 3 (4.7%), one was grade 4 (1.2%), and one was grade 5 (1.2%). The incidence of severe ED (International Index of Erectile Dysfunction-5 score 5-10) was 14% pre-HIFU, and 51.9% and 82.3% pre- and post-SRT, respectively. Because our study was retrospective, results have to be interpreted cautiously. CONCLUSIONS: SRT provides satisfactory oncologic control after HIFU failure with little (or mild) additional toxicity. These results warrant further investigation.

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy.

Ultrafractionation of radiation therapy is a novel regimen consisting of irradiating tumors several times daily, delivering low doses (<0.75 Gy) at which hyperradiosensitivity occurs. We recently demonstrated the high efficiency of ultrafractionated radiotherapy (RT) on glioma xenografts and report here on a phase II clinical trial to determine the safety, tolerability, and efficacy of an ultrafractionation regimen in patients with newly and inoperable glioblastoma (GBM). Thirty-one patients with histologically proven, newly diagnosed, and unresectable supratentorial GBM (WHO grade IV) were enrolled. Three daily doses of 0.75 Gy were delivered at least 4 hours apart, 5 days per week over 6-7 consecutive weeks (90 fractions for a total of 67.5 Gy). Conformal irradiation included the tumor bulk with a margin of 2.5 cm. The primary end points were safety, toxicity, and tolerability, and the secondary end points were overall survival (OS) and progression-free survival (PFS). Multivariate analysis was used to compare the OS and PFS with the EORTC-NCIC trial 26981-22981/CE.3 of RT alone vs radiation therapy and temozolomide (TMZ). The ultrafractionation radiation regimen was safe and well tolerated. No acute Grade III and/or IV CNS toxicity was observed. Median PFS and OS from initial diagnosis were 5.1 and 9.5 months, respectively. When comparing with the EORTC/NCIC trial, in both PFS and OS multivariate analysis, ultrafractionation showed superiority over RT alone, but not over RT and TMZ. The ultrafractionation regimen is safe and may prolong the survival of patients with GBM. Further investigation is warranted and a trial associating ultra-fractionation and TMZ is ongoing.

Inter-clinician variability in making dosimetric decisions in pediatric treatment: a balance between efficacy and late effects.

PURPOSE: To investigate variability of clinical target volume (CTV) delineation and deviations according to doses delivered in normal tissue for abdominal tumor irradiation in children. MATERIAL AND METHODS: For a case of nephroblastoma six French pediatric radiation oncologists outlined post-operative CTV, on the same dosimetric CT scan according to the International Society for Pediatric Oncology 2001 protocol. On a reference CTV and organs at risk (OAR), we performed dosimetric planning with the constraints as 25.2 Gy for CTV, V(20 max) to 50% for liver, V(12) <15% for kidney. Data were analyzed with Aquilab software. RESULTS: Final CTVs showed inter-clinician variability: 44.85-120.78 cm(3). The recommended liver doses were not respected in four cases: V(20) from 74% to 88% of the volume; for kidney, in two cases: V(12) of 17.6% and 25%, respectively. For vertebral bodies, no deviations were noted. CONCLUSION: Variability not only affected CTV delineation but also dose distribution to OAR with different compromises. This practice training demonstrates the hudge lack of data about correlation between dose, volume and risk of late effects in pediatric radiotherapy. We intend to record prospectively the dose/volume histogram of each OAR in a national database in order to characterize late effects occurring in relation to treatment modalities.

Online quality control, hyperfractionated radiotherapy alone and reduced boost volume for standard risk medulloblastoma: long-term results of MSFOP 98.

PURPOSE: To determine event free and overall survival, and long-term cognitive sequelae of children with standard-risk medulloblastoma (SRM) treated with hyperfractionated radiotherapy, conformal reduced boost volume without chemotherapy, and online quality assurance. PATIENTS AND METHODS: Forty-eight patients (age 5 to 18 years) were included in the Medulloblastoma-Société Française d'Oncologie Pédiatrique (MSFOP 98) protocol (December 1998 to October 2001). Patients received hyperfractionated radiotherapy (HFRT; 36 Gy, 1 Gy/fraction twice per day) to the craniospinal axis followed by a boost to the tumor bed (1.5-cm margin) to a dose of 68 Gy. Records of craniospinal irradiation were reviewed before treatment started. Neuropsychologic evaluations were done according to the protocol (1, 3, 5, and 7 years after irradiation). Cognitive outcomes were followed longitudinally with full-scale intelligence quotient (FSIQ) obtained with age-adapted Wechsler scales. RESULTS: After a median follow-up of 77.7 months, 6-year overall survival (OS) and event-free survival (EFS) rates for the cohort were 78% (95% CI, 66% to 90%) and 75%, respectively (95% CI, 62% to 87%). Thanks to quality control, 14 major deviations were detected. Annual full scale IQ decline was 2 points over a 6-year period. Predicted change in FSIQ points per year was 2.15 (95% CI, -1.24 to 3.51) with an intercept (ie, predicted FSIQ) of 93.57 at baseline. CONCLUSION: HFRT protocol with conformal reduced boost and online quality control allows excellent long-term OS and EFS in the absence of chemotherapy. In addition, FSIQ drops seem to be less pronounced than previously reported with standard irradiation regimens.

[Prostate carcinoma in the elderly]. / Le cancer de la prostate du sujet âgé.

Prostate carcinoma is the most frequent cancer in French men. Prostate carcinoma in elderly is the topic of this review. The review included chapters on age as the main factor for prostate carcinoma, the modification of disease presentation or PSA level depending on age, and then the challenge of age in therapeutic decisions. Finally, we evaluate the place of elderly patients in prospective trials and in adjustable therapies.

Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults.

PURPOSE: To assess prognostic factors for adults with medulloblastoma in a multicenter, retrospective study. METHODS AND MATERIALS: Data were collected by file review or mail inquiry for 253 adults treated between 1975 to 2004. Radiologists or surgeons assessed disease characteristics, such as volume and extension. Patients were classified as having either high- or standard-risk disease. Prognostic factors were analyzed. RESULTS: Median patient age was 29 years. Median follow-up was 7 years. Radiotherapy was delivered in 246 patients and radiochemotherapy in 142. Seventy-four patients relapsed. Respective 5- and 10-year overall survival rates were 72% and 55%. Univariate analysis showed that survival significantly correlated with metastasis, postsurgical performance status, brainstem involvement, involvement of the floor of the fourth ventricle (V4), and radiation dose to the spine and to the posterior cerebral fossa (PCF). By multivariate analysis, brainstem, V4 involvement, and dose to the PCF were negative prognostic factors. In the standard-risk subgroup there was no overall survival difference between patients treated with axial doses of >or=34 Gy and patients treated with craniospinal doses <34 Gy plus chemotherapy. CONCLUSION: We report the largest series of medulloblastoma in adults. Prognostic factors were similar to those observed in children. Results suggest that patients with standard-risk disease could be treated with radiochemotherapy, reducing doses to the craniospinal area, maintaining at least 50 Gy to the PCF. The role of chemotherapy for this group is still unclear. A randomized study should be performed to confirm these results, but because frequency is very low, such a study would be difficult.

[Bone metastatic evolution of a recurrent meningioma: case report]. / Evolution métastatique osseuse d'un méningiome récidivant: à propos d'un cas.

We report the case of a 57-year-old man who presented with two local recurrences and metastatic dissemination of a papillary meningioma of the sphenoid 3 years after surgery. Treatment consisted in a combination of surgery for the local recurrence in the initial site, radiotherapy and chemotherapy for bone metastases. Evolution of the disease spread over 7.5 years. The literature relating metastatic meningiomas is reviewed; prognostic factors and main therapeutic protocols are discussed.

Twenty years' experience in the treatment of acoustic neuromas with fractionated radiotherapy: a review of 45 cases.

PURPOSE: To evaluate very long-term results of fractionated radiotherapy (FRT) of acoustic neuromas (AN). METHODS AND MATERIALS: From January 1986 to January 2004, FRT was performed in 45 consecutive patients (46 AN). Indications were as follows: poor general condition contraindicating surgery, hearing preservation in bilateral neuromas, partial resection, nonsurgical recurrence. A 3-field to 5-field technique with static beams was used. A mean total dose of 51 Gy was given (1.80 Gy/fraction). The median tumor diameter was 31 mm (range, 11-55 mm). The median follow-up from FRT was 80 months (range, 4-227 months). RESULTS: The particularity of our series consists of a very long-term follow-up of FRT given to selected patients. Nineteen patients died, two with progressive disease, and 17 from non-AN causes. A serviceable level of hearing was preserved in 7/9 hearing patients. No patient had facial or trigeminal neuropathy. Tumor shrinkage was observed in 27 (59%) and stable disease in 16 (35%). Tumor progression occurred in three patients, 12 to 15 months after FRT. Two additional tumors recurred after shrinkage 20 and 216 months after treatment and were operated on. Actuarial local tumor control rates at 5 and 15 years were 86%. For the patient who had a tumor recurrence at 216 months, histologic examination documented transformation to a low-grade malignant peripheral nerve sheath tumor. CONCLUSION: Very long-term efficacy of FRT is well documented in this series. However, our results suggest that malignant transformation can occur many years after FRT so we advocate caution when using this treatment for young patients.

Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol.

PURPOSE: Between December 1998 and October 2001, patients <19 years old were treated for standard-risk medulloblastoma according to the Medulloblastome-Société Française d'Oncologie Pédiatrique 1998 (M-SFOP 98) protocol. Patients received hyperfractionated radiotherapy (36 Gy in 36 fractions) to the craniospinal axis, a boost with conformal therapy restricted to the tumor bed (to a total dose of 68 Gy in 68 fractions), and no chemotherapy. Records of craniospinal irradiation were reviewed before treatment start. RESULTS: A total of 48 patients were considered assessable. With a median follow-up of 45.7 months, the overall survival and progression-free survival rate at 3 years was 89% and 81%, respectively. Fourteen major deviations were detected and eight were corrected. No relapses occurred in the frontal region and none occurred in the posterior fossa outside the boost volume. Nine patients were available for volume calculation without reduction of the volume irradiated. We observed a reduction in the subtentorial volume irradiated to >60 Gy, but a slight increase in the volume irradiated to 40 Gy. No decrease in intelligence was observed in the 22 children tested during the first 2 years. CONCLUSION: This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children. Moreover, intellectual function seemed to be preserved. These results are promising.

Incidence of central nervous system tumors in Gironde, France.

The incidence of CNS tumors is subject to geographical and temporal variations which are poorly understood. The incidence of these tumors was studied in Gironde, a department of southwestern France with 1,058,911 inhabitants older than 16 years. We recorded any malignant or benign central nervous system (CNS) tumor diagnosed between May 1999 and April 2001 in adults living in Gironde. Three hundred and twenty-nine CNS tumors were diagnosed during the study period. The incidence of CNS tumors in adults was therefore 15.5 per 100,000. Overall, the incidence according to sex was 14.7 for males and 16.2 per 100,000 for females. The incidence rate increased according to age up to 80 years (3.7 per 100,000 for 20-29 years of age to 33.4 per 100,000 for 70-79 years of age) and reduced thereafter for gliomas. Our estimation of the incidence of CNS tumors ranks high among the earlier reports. Further analytic studies are ongoing.