Clinical criteria and diagnostic assessment of fibromyalgia: position statement of the Italian Society of Neurology-Neuropathic Pain Study Group.

BACKGROUND: The role of central and/or peripheral nervous system dysfunction is basically fundamental in fibromyalgia. AIM: The aim of this position statement on behalf of the Neuropathic Pain Study Group of the Italian Society of Neurology is to give practical guidelines for the clinical and instrumental assessment of fibromyalgia (FM) in the neurological clinical practice, taking into consideration recent studies. METHODS: Criteria for study selection and consideration were original studies, case-controls design, use of standardized methodologies for clinical practice, and FM diagnosis with ACR criteria (2010, 2011, 2016). RESULTS: ACR criteria were revised. For diagnostic procedure of small-fiber pathology, 47 studies were totally considered. Recent diagnostic criteria should be applied (ACR, 2016). A rheumatologic visit seems mandatory. The involvement of small fibers should request at least 2 among HRV + SSR and/or laser-evoked responses and/or skin biopsy and/or corneal confocal microscopy, eventually followed by monitoring of metabolic and/or immunological/ and or/paraneoplastic basis, to be repeated at 1-year follow-up. CONCLUSIONS: The correct diagnostic approach to FM could promote the exclusion of the known causes of small-fiber impairment. The research toward common genetic factors would be useful to promote a more specific therapeutic approach.

A multi-institutional analysis of fractionated versus single-fraction stereotactic body radiotherapy (SBRT) in the treatment of primary lung tumors: a comparison between two antipodal fractionations.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) is a consolidate treatment for inoperable early-stage lung tumors, usually delivered in single or multi-fraction regimens. We aimed to compare these two approaches in terms of local effectiveness, safety and survival. MATERIALS AND METHODS: Patients affected by medically inoperable early-stage lung tumor were treated at two Institutions with two different schedules: 70 Gy in ten fractions (TF) (BED10: 119 Gy) or 30 Gy in single fraction (SF) (BED10: 120 Gy). RESULTS: 73 patients were treated with SBRT delivered with two biological equivalent schedules: SF (44) and TF (29). The median follow-up was 34 months (range 3-81 months). Three-year Overall survival (OS) was 57.9%, 3-year cancer-specific survival (CSS) was 77.2%, with no difference between treatment groups. Three-year progression-free survival (LPFS) was 88.9% and did not differs between SF and TF. Overall, four cases (5.4%) of acute grade ≥ 3 pneumonitis occurred. No differences in acute and late toxicity between the two groups were detected. CONCLUSION: SF and TF seems to be equally safe and effective in the treatment of primary inoperable lung tumors especially for smaller lesion. The SF may be preferentially offered to reduce patient access to hospital with no negative impact on tumor control and survival.

Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy.

OBJECTIVES: To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line treatment with androgen receptor-targeted therapy (ARTT). PATIENTS AND METHODS: Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analysis (MVA) were performed. RESULTS: Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio [HR] 3.66, p = 0.009; HR 3.03, p = 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23, p = 0.017; HR 0.19, p = 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39, p = 0.026; HR 2.79, p = 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity. CONCLUSION: Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed.

Markers of Cardiotoxicity in Early Breast Cancer Patients Treated With a Hypofractionated Schedule: A Prospective Study.

PURPOSE: To evaluate, in a series of early breast cancer (BC) patients treated with hypofractionated adjuvant radiotherapy (RT), whether N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I assay measurements can predict acute clinical or preclinical cardiotoxicity. PATIENTS AND METHODS: The study comprised 44 consecutive patients, who underwent conservative surgery with or without (neo)adjuvant chemotherapy and hypofractionated adjuvant RT. The RT schedule consisted in a total dose of 42.4 Gy in 16 fractions administered 5 days per week. Twenty-one patients received a subsequent boost to the tumor bed consisting of a total dose of 10 Gy in 4 fractions delivered via a direct electron field. All patients underwent 12-lead electrocardiogram, echocardiogram, and cardiac clinical examinations before RT to assess cardiovascular risk factors; these examinations were repeated yearly for 5 consecutive years. High-sensitivity cardiac troponin I and NT-proBNP were analyzed from serum samples at baseline, after delivery of the fourth and 16th RT fractions, and 12 months after treatment completion. RESULTS: No increase in cardiac troponin I and B-type natriuretic peptide levels related to left breast irradiation was observed. No statistical difference in NT-proBNP and high-sensitivity troponin I levels between left- and right-sided BC was found. An increase was observed of B-type natriuretic peptide levels at baseline, during treatment, and until 12 months after RT related to hypertension, with the P value near to the .05 threshold for age and chemotherapy. CONCLUSION: Conformational hypofractionated RT in left-sided BC may not cause acute myocardial damage. Early cardiac screening may be used to identify patients with cardiologic risk factors, patients who are older than 60 years, and patients who received chemotherapy that could result in clinically relevant cardiac pathologies.

Diagnosis of pediatric anti-NMDAR encephalitis at the onset: A clinical challenge.

BACKGROUNDS: To investigate the clinical and instrumental features at the onset addressing to the diagnosis of anti-NMDAR encephalitis. METHODS: Twenty children (age: 15 months-17 years; 7 males, 13 females) with initial suspected diagnosis of autoimmune encephalitis, observed between January 2008 and March 2018, were included. The final diagnosis was anti-NMDAR encephalitis in 7 children, other/probable autoimmune encephalitis in 7 children, and primary psychosis in the remaining 6 children. RESULTS: At the clinical onset, anxiety disorder was the main symptom that helped in distinguishing the group of psychotic children from children with non-infectious encephalitis (P = 0.05 OR = 0.001), while epileptic seizures strongly predicted anti-NMDAR encephalitis (P = 0.04 OR = 28.6). At the onset, anti-NMDAR encephalitis could be distinguished from other/probable autoimmune encephalitis for the presence of sleep/wake rhythm alteration (P = 0.05 OR = 15). Among the symptoms occurring during the hospitalization, movement disorders (P = 0.031 OR = 12) were predictive of non-infectious encephalitis rather than primary psychosis. More specifically, the occurrence of language impairment (P = 0.03 OR = 33), epileptic seizures (P = 0.04 OR = 28.6) and catatonia (P = 0.03, OR = 33), were predictive of anti-NMDAR encephalitis. Also at this stage, anxiety disorder (P = 0.03 OR = 0.033) was predictive of primary psychosis. CONCLUSION: Our findings suggest that at the clinical onset epileptic seizures and sleep/wake rhythm alteration represent the main features addressing to the diagnosis of anti-NMDAR encephalitis rather than primary psychosis and other/probable autoimmune encephalitis, while anxiety disorder could be a solid predictor of primary psychosis.

Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer.

The aim of this observational study is to investigate whether local consolidative treatment delivered to the primary site and metastatic tumour burden may add survival benefit to de novo oligometastatic prostate cancer (Oligo-PCa) patients. We retrospectively reviewed all Oligo-PCa patients treated with radiotherapy to the primary tumor sites and metastatic tumor burden at our institution between March 2010 and June 2019. All patients having ≤ 5 metastases involving nodes and/or bones, loco-regional and/or extra-pelvic sites, were included. Most of the patients had started androgen deprivation therapy with or without docetaxel as standard of care before radiotherapy. The Kaplan Meier analysis was performed to estimate survival outcomes. The univariate analysis tested possible prognostic factors increasing the rate of biochemical relapse. We analysed 37 Oligo-PCa patients. Twenty-eight (75.7%) had loco-regional metastases, in 9 patients (24.3%) the metastatic tumour burden was extra-pelvic. Nineteen (51.4%) had bone metastases, 21 (56.8%) nodal involvement and 7 (18.9%) both. Twenty (54.1%) had a single metastasis. The median follow-up was 55.5 months. The median overall survival (OS) was 68.8 months, the 2- and 5-year OS rates were 96.9% and 65.4%. The median biochemical relapse free survival (b-RFS) was 58 months and the 2- and 5-year b-RFS rates were 73.3% and 39.3%. The 2- and 5-year local relapse free survival rates were 93.9% and 83.7%. On the univariate analysis post-treatment PSA level ≤ 1 ng/ml was significantly related with the b-RFS (p = 0.004). Curative approach in Oligo-PCa patients involving both the primary tumor and metastatic sites may be feasible and well tolerate. Many patients presented longer survival and PSA at first follow-up was the most important prognostic factor. Further trials are needed to confirm our results and to evaluate if patients with PSA at first follow-up > 1 ng/ml may benefit from further treatments.

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

Salvage radiotherapy with simultaneous integrated boost in non small-cell lung cancer patients with mediastinal relapse after surgery: a pilot study.

BACKGROUND: The aim of our study was to evaluate feasibility, toxicity profile and local control of salvage intensity modulated radiotherapy (IMRT) delivered with simultaneous integrated boost (SIB) associated or not to concomitant weekly cisplatin in patients affected by NSCLC with mediastinal nodal recurrence after surgery. Patterns of recurrence, outcomes and prognostic factors were assessed. METHODS: Fourteen consecutive patients received 25 fractions of 50Gy/2Gy to the elective nodal stations and boost up to 62.5Gy/2.5Gy to the macroscopic lymph node metastases. Concomitant weekly cisplatin (40 mg/m2) was administered to 8 (57.1%) patients. RESULTS: Five (35.7%) patients experienced grade 2 pneumonitis and 5 (35.7%) patients had grade 2 esophagitis. One case of grade 3 pneumonitis occurred and was successfully treated with antibiotics and steroids with no sequelae. No patient recurred locally in the boost volume (local control 100%). Loco-regional control was 79% with 3 patients that developed nodal recurrence principally marginal to the elective volume. Seven patients developed distant metastases. Median PFS was 7 months. The nodal involvement of station 7 was associated to a significantly lower median metastasis-free survival (4 months vs. not reached, p = 0.036). CONCLUSIONS: Salvage radiotherapy with IMRT-SIB is a feasible and a well-tolerated treatment option for mediastinal recurrent NSCLC after surgery. The role of more intensified radiation regimens and association to systemic therapy remain to be evaluated in larger cohorts.

30 Gy single dose stereotactic body radiation therapy (SBRT): Report on outcome in a large series of patients with lung oligometastatic disease.

OBJECTIVES: To evaluate the local control (LC) and long term adverse effects in a series of patients with lung metastases who received 30 Gy in single dose with stereotactic technique. MATERIALS AND METHODS: Between December 2008 and April 2016, a total of 166 lung metastases in 129 patients affected by oligometastatic disease were treated at our Institution with stereotactic body radiotherapy (SBRT). Mainly, the primary tumors were non small-cell lung cancer and colorectal cancer (45.2% and 28.8%, respectively). Prognostic factors were also assessed. RESULTS: The median follow-up was 38 months. Local progression occurred in 24 (14.4%) lesions in 21 patients. Intra-thoracic progression (new lung lesions or thoracic lymph node metastases) occurred in 59 (45.7%) patients. Forty-five (34.8%) patients had distant progression after a median time of 14 months. The 3- and 5-years local relapse-free survival (LPFS) were 80.1% and 79.2% (median not reached), respectively. One-hundred forty-eight patients were evaluated for late toxicity (follow-up >6 months): 51 (34.4%) patients had grade ≤2 fibrosis, 11 (7.4%) patients experienced grade 3 fibrosis. Two (1.3%) cases of rib fracture occurred. One case of toxic death (grade 5) has been reported. Median OS was 39 months. At the univariate analysis, lesion diameter ≤18 mm correlated significantly with a longer LPFS (p = 0.001). At the multivariate analysis, lesion diameter <18 mm was predictive for longer LPFS (p = 0.006). Also, oligometastases from primary colorectal cancer was a significant predictive factor for worse LPFS (p = 0.041) and progression-free survival (p = 0.04). CONCLUSIONS: To our knowledge, the current study represents the largest series on the use of SBRT 30 Gy single dose for lung metastases. Our results confirm the effectiveness and safety of this schedule administered in selected oligometastatic patients. Further prospective series could better validate these results.

Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials.

BACKGROUND: In the neurophysiological assessment of patients with neuropathic pain, laser evoked potentials (LEPs), contact heat evoked potentials (CHEPs) and the evoked potentials by the intraepidermal electrical stimulation via concentric needle electrode are widely agreed as nociceptive specific responses; conversely, the nociceptive specificity of evoked potentials by surface concentric electrode (SE-PREPs) is still debated. METHODS: In this neurophysiological study we aimed at verifying the nociceptive specificity of SE-PREPs. We recorded LEPs, CHEPs and SE-PREPs in eleven healthy participants, before and after epidermal denervation produced by prolonged capsaicin application. We also used skin biopsy to verify the capsaicin-induced nociceptive nerve fibre loss in the epidermis. RESULTS: We found that whereas LEPs and CHEPs were suppressed after capsaicin-induced epidermal denervation, the surface concentric electrode stimulation of the same denervated skin area yielded unchanged SE-PREPs. CONCLUSION: The suppression of LEPs and CHEPs after nociceptive nerve fibre loss in the epidermis indicates that these techniques are selectively mediated by nociceptive system. Conversely, the lack of SE-PREP changes suggests that SE-PREPs do not provide selective information on nociceptive system function. SIGNIFICANCE: Capsaicin-induced epidermal denervation abolishes laser evoked potentials (LEPs) and contact heat evoked potentials (CHEPs), but leaves unaffected pain-related evoked potentials by surface concentric electrode (SE-PREPs). These findings suggest that unlike LEPs and CHEPs, SE-PREPs are not selectively mediated by nociceptive system.

Trigeminal laser-evoked potentials: a neurophysiological tool to detect post-surgical outcome in trigeminovascular contact neuralgia.

BACKGROUND: The aim of this study was to explore the nociceptive system of patients affected by trigeminal neuralgia (TN) secondary to documented vascular contact who underwent microvascular decompression. For that purpose, we used the classical trigeminal reflexes and the trigeminal laser-evoked potentials (tLEPs) before and after surgery, in order to verify any possible change after decompression and determine if there was any correlation between the neurophysiological parameters and the clinical outcome. METHODS: Eleven patients affected by TN caused by trigeminovascular contact and 10 age-matched controls underwent conventional trigeminal reflexes (bilateral Blink Reflex/BR and Masseter Inhibitory Reflex stimulating infraorbital and mental nerves/MIR V2 and V3) and tLEPs. Patients repeated neurophysiological tests one week after surgery. RESULTS: Short-latency BR and MIR were normal in all patients before surgery and there was no statistical difference before and after surgery. Conversely, in patients before surgery, tLEPs' amplitudes were significantly lower in the affected than in the healthy side (p = 0.017 for V2 and 0.037 for V3 branches). After surgery, on the affected side, tLEP amplitude increased and the pre/post-operative difference was significant (p = 0.017 for V2 and 0.028 for V3 divisions). Nine patients referred satisfactory pain relief and the favourable clinical outcome correlated with the neurophysiological recovery. CONCLUSIONS: This study demonstrates that TN caused by trigeminovascular compression may be related to Aδ fibres impairment, and tLEPs are more sensitive than conventional trigeminal reflexes to reveal small fibre dysfunction and to monitor the post-surgical outcome in these patients.

External-beam radiotherapy and/or HDR brachytherapy in postoperative endometrial cancer patients: clinical outcomes and toxicity rates.

PURPOSE: The objectives of this study were to evaluate local disease control, overall survival (OS), disease-free survival (DFS) and local relapse-free survival (LRFS) in patients with endometrial cancer undergoing adjuvant vaginal brachytherapy (VBT )± external-beam radiotherapy (EBRT). MATERIALS AND METHODS: From September 2007 to February 2011, 40 patients with endometrial cancer were retrospectively analysed. Surgery consisted of total hysterectomy and bilateral salpingo-oophorectomy without node dissection (16 patients) or with bilateral pelvic node dissection (24 patients). The stage distribution was as follows: two IA, nine IB, 12 IC, five IIA, eight IIB, two IIIA and two IIIC. Thirty-four patients underwent EBRT and VBT. Six patients received VBT alone. RESULTS: Median follow-up was 26 months. The 5-year OS and DFS were 96.4% and 86.9%, respectively. No local recurrence was observed. Four patients presented distant disease (three had lung metastases and one had hepatic node metastases). Acute EBRT-related toxicities were seen in 15 (38%) patients. We recorded late toxicities in 14 patients (35%). There was no evidence of grade 3-4 toxicity. CONCLUSIONS: Adjuvant EBRT and/or VBT in patients with endometrial cancer showed good outcomes in terms of local disease control, with an acceptable toxicity profile.

Adenoid cystic carcinoma of Bartholin's gland receiving adjuvant radiation therapy: case report.

Adenoid cystic carcinoma (ACC) of Bartholin's gland is an extremely rare tumor of the female genital tract, representing about 5%-15% of Bartholin's gland malignancies. Approximately 80 cases have been reported in the literature. The authors describe the case of a 54-year-old woman with locally advanced ACC of Bartholin's gland treated with surgery and adjuvant radiotherapy (RT). She underwent radical hemivulvectomy associated with ipsilateral inguinal and femoral lymph node dissection. Subsequently, she received postoperative three-dimensional conformal RT. Total dose prescribed was 56 Gy in 28 fractions of two Gy each. After 20 months of follow up, there was no evidence of local failure or distant progression.

Acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with concurrent cetuximab and radiotherapy.

PURPOSE: The authors report acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with radiotherapy and cetuximab. MATERIALS AND METHODS: Data collection was performed prospectively on patients treated from September 2007 to March 2009. Treatment consisted of 64.8-70 Gy radiotherapy in conventional fractions and cetuximab. RESULTS: Two out of 14 patients did not complete the planned combined treatment; radiotherapy was temporarily suspended in six other patients. Seven of 12 patients received cetuximab until the end of radiotherapy. Treatment breaks were principally due to severe acute cutaneous or mucous toxicity. Any grade acneiform rash occurred in all patients. In-field G3-4 cutaneous toxicity occurred in five (36%) patients and G3-4 mucous toxicity in seven (50%). One patient died of sepsis. CONCLUSIONS: In our experience, severe acute toxic reactions are common in patients treated with radiotherapy and concurrent cetuximab, resulting in frequent breaks or incomplete treatment with potential reduction in disease control.

Subjective and objective measures of late genitourinary morbidity following hypofractionated radiotherapy in men with prostate cancer.

To value the late genitourinary (GU) morbidity in men treated with a hypofractionated radiotherapy regimen for prostate cancer. Patients with intermediate risk factors according to D'Amico's criteria were selected. The hypofractionated schedule consisted of 15 fractions of 3.63 Gy delivered three times per week for a total dose of 54.3 Gy. Significant changes in storage-symptoms were not found. A significant transient worsening in the score of late effects of normal tissue late effects normal tissue task force (LENT)-subjective, objective, management, analytic (SOMA) urinary-function domain was observed at 12 months with subsequent improvement at 28 months. The assessment of voiding-symptoms and maximum urinary flow rate (Qmax) showed that no significant difference was measurable at 12 and 28 months. For PVR, a transient increase at 12 months with a subsequent decrease at 28 months was measured. No significant increase in alpha-blockers usage and in the percentage of men with pathological nonintubated uroflowmetry (NIF) was observed at 12 and 28 months. Finally, patients did not perceive any clinical worsening in their quality of life (QoL) as attested by the International Prostate Symptom Score (IPSS)-QoL. Our study seems to suggest that our hypofractionated radiotherapy schedule for the treatment of prostate cancer is safe in terms of late urinary morbidity. Further study will be required to confirm our results.

Lower eyelid ablative fractional resurfacing: a new technique to treat skin laxity and photoaging.

AIM: The authors describe and validate a new technique of one-session, multiple-pass, low spot density, fractional ablative CO2 resurfacing in order to treat lower eyelid skin laxity and photoaging. METHODS: The investigation was conducted on 25 patients. The YouLaser CO2 (Quanta System s.p.a., Italy), a 10600-nm CO2 ablative fractional laser system, was used to treat the lower eyelids at a pulse energy of 25 to 35 J, with a pulse duration of 1 ms, 200 microm spot size and a density of 100 laser spots/cm2 for every passage. Each patient had 1 session only, and 1 to 3 passes per area, after application of topical anesthesia. Two blinded physicians assessed eyelid tightening from photographs of 25 patients using a 4-point evaluation scale (1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%. The grades of the 2 evaluating physicians were analyzed using t-test and Kruskal-Wallis analysis of variance. The same evaluation scale was used to assess patient satisfaction in a questionnaire. RESULTS: The median grades of the 2 physicians for all patients did not differ significantly (p = .88) from one another, and the Kruskal-Wallis assessment (p = 0.0011) indicated unbiased grading among the physicians. All patients achieved a degree of eyelid tightening; 8% achieved 1% to 25% improvement, 24% achieved 25% to 50%, 40% achieved 50% to 75%, and 28% achieved 75% to 100%. Results of patient questionnaires were similar to that of the physicians' evaluation: 4% achieved 1% to 25% improvement, 28% achieved 25% to 50%, 48% achieved 50% to 75%, and 20% achieved 75% to 100%. CONCLUSIONS: The fractioned form of CO2 laser delivery offers very good results with short downtime and easy patient recuperation. The new technique allowed the operator to control skin contraction immediately after laser skin exposure. Using high energy and lower laser spot density permits a control of the amount of contraction simply by the number of passes. Increasing this variable progressively increased skin damage and consequently the contraction.

Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma.

OBJECTIVES: The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide. PATIENTS AND METHODS: Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status (KPS) > or = 60 were treated with hypofractionated RT (6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks) followed by up to 12 cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28 day cycle). The HRQOL was assessed with the EORTC Quality of Life Questionnaire C30. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), toxicity and quality of life. RESULTS: The median OS was 9.3 months and the median PFS was 6.3 months. The 6 and 12 month survival rates were 86% and 35%, respectively. The 6 and 12 month PFS rates were 55% and 12%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.008). Neurological deterioration occurred during or after RT in 16% of patients and was resolved in most cases with the use of steroids. Grade 3-4 hematologic toxicity occurred in 28% of patients during the adjuvant chemotherapy treatment with temozolomide. The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time. CONCLUSIONS: Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients.

OBJECTIVES: The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. PATIENTS AND METHODS: 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) > or = 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m(2) per day followed by six cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. RESULTS: The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3-4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. CONCLUSIONS: Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.