Cystemustine in recurrent high grade glioma

Summary In this study, we have assessed the efficacy of a nitrosourea, cystemustine, in treating patients with recurrent high grade glioma with overall survival analysis as primary end-point. Forty-eight patients with recurrent high grade glioma (24 glioblastomas, 17 astrocytomas and 5 oligodendrogliomas) were treated every 2 weeks with 60 mg/m² cystemustine by a 15 min-infusion. The median number of treatment cycles was 4 (range 1–17). The median overall survival was 8.3 months (range 1–97) and the 6- and 12-month overall survival rates were 55.3% (95% CI, 41.3–68.6%) and 29.8% (95% CI, 18.6–44.0%), respectively. The objective response rate was 18.8% (95% CI, 7.7–29.9%), and 54.2% of patients had stable disease (95% CI, 40.1–68.3%). Multivariate analysis showed that WHO performance status, histology and response to cystemustine were significant prognostic factors for survival of patients with recurrent glioma.In conclusion, cystemustine has encouraging activity for patients with recurrent high grade glioma.An erratum to this article can be found at     

Osmotic blood–brain barrier disruption chemotherapy for diffuse pontine gliomas

Summary The prognosis for patients with diffuse pontine gliomas (DPG) remains poor. New aggressive innovative treatments are necessary to treat this disease. From 1984 to 1998, eight patients (4M/4F), median age 11 years, with DPG were treated with monthly osmotic blood–brain barrier disruption (BBBD) chemotherapy using intraarterial carboplatin or methotrexate and intravenous cytoxan and etoposide. Patients presented for a median duration of 6 weeks with increased intracranial pressure, long tract signs, diplopia, ataxia, and nausea/vomiting. DPG was demonstrated on magnetic resonance (MR) imaging in seven patients and on CT in one. Two patients had biopsies that showed an astrocytoma and an anaplastic astrocytoma. Three tumors enhanced on MR imaging after contrast administration. Three patients had radiation therapy before BBBD chemotherapy and four afterwards. Two patients had chemotherapy (tamoxifen, topotecan) before BBBD chemotherapy and two afterwards. In general, patients were evaluated with MR imaging every 3 months to monitor for a response to treatment. The median number of chemotherapy cycles that were administered by BBBD was 10, mean 10. Three patients also received one, two, or three cycles of intraarterial chemotherapy without BBBD. One patient that was started on carboplatin was converted to methotrexate, and five that were started on the methotrexate protocol were later converted over to carboplatin. One patient received monthly methotrexate followed by 14 days of procarbazine and one patient started on methotrexate was switched to navelbine. MR imaging demonstrated two partial responses, five patients with stable disease, and one with disease progression. The median time to tumor progression was 15 months with the range from <1 to 40 months. The median survival from the time of diagnosis was 27 months, ranging from 7 to 80 months. The median survival time from the first BBBD or intraarterial treatment was 16.5 months, ranging from 5 to 69 months. One patient was lost to follow-up with an unknown date of death. Although the sample size is small, the TTP and survival times are longer than those previously reported in other DPG series. In addition, the ability to demonstrate stable disease or partial responses in DPG on MR imaging argues for the therapeutic benefit of BBBD chemotherapy. The enhanced delivery of chemotherapy afforded by osmotic BBBD supports the further examination of this treatment modality for patients with DPG.     

Young age may predict a better outcome for children with diffuse pontine glioma

BACKGROUND: Because diffuse pontine glioma (DPG) is rare among young children, the outcome of affected patients is unknown. METHODS: The authors reviewed clinical and radiologic characteristics of all children aged <3 years with DPG who were evaluated at their institution. Inclusion followed standard magnetic resonance imaging criteria for the diagnosis of DPG. RESULTS: The median age at diagnosis in 10 patients was 2.2 years (range, 0.8-2.7 years). The median interval between the onset of symptoms and diagnosis was 2.5 months. All patients presented with cranial nerve palsy with (n = 7) or without (n = 3) other neurologic deficits attributable to brainstem involvement. All patients had pons-based tumors involving >50% of this brainstem segment. Histologic confirmation was attempted in 2 patients who had atypical radiologic features at diagnosis. Four patients initially were observed only. All patients received therapy, which consisted of radiation therapy (RT) (n = 2), RT and chemotherapy (n = 6), or chemotherapy only (n = 2). Four patients died of tumor progression after a median of 0.7 years (range, 0.5-3.7 years). Six patients have survived for a median of 2.3 years (range, 0.9-8 years). The 3-year progression-free and overall survival rates were 45% +/- 19% and 69% +/- 19%, respectively. CONCLUSIONS: Children aged <3 years with DPG potentially may fare better than older patients with the same diagnosis despite the use of similar therapy. The current results suggested that DPG in younger children may be distinct biologically from similar tumors in older age groups.     

High-dose radiotherapy to 78 Gy with or without temozolomide for high grade gliomas

Objectives To describe outcomes associated with high-dose radiotherapy with and without temozolomide for high grade central nervous system (CNS) neoplasms. Methods Retrospective chart review of 60 patients diagnosed with malignant glioma treated with ≥70 Gy radiotherapy. Results Median age at diagnosis was 52 years, and 52 patients had astrocytomas (38 glioblastomas). Median prescribed radiotherapy dose was 78 Gy (range 70–80), and 29 patients received concurrent temozolomide. Eighty-six percent completed the planned course treatment. Three patients experienced RTOG grade 3 acute CNS toxicity; late brain necrosis was suspected in four patients. Overall median survival was 13 months (range 2–83). Within glioblastoma patients, temozolomide provided a statistically significant survival improvement over no chemotherapy (median survival 12.7 vs. 7.5 months; P = 0.0058). Conclusions High dose conformal radiotherapy to ≥70 Gy with chemotherapy for high-grade CNS neoplasms appears safe but survival remains suboptimal. Within glioblastoma patients, temozolomide provided statistically significant survival improvement over no chemotherapy.     

Dose dense 1 week on/1 week off temozolomide in recurrent glioma: a retrospective study

Alternative temozolomide regimens have been proposed to overcome O⁶-methylguanine-DNA methyltransferase mediated resistance. We investigated the efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression of a glioblastoma during or after chemo-radiation with temozolomide or a recurrence of another type of glioma after radiotherapy and at least one line of chemotherapy. Patients received ddTMZ at 100–150 mg/m²/d (days 1–7 and 15–21 in cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the response was assessed by MRI using the RANO criteria; complete and partial responses were considered objective responses. Fifty-three patients were included. The median number of cycles of ddTMZ was 4 (range 1–12). Eight patients discontinued chemotherapy because of toxicity. Two of 24 patients with a progressive glioblastoma had an objective response; progression free survival at 6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma without combined 1p and 19q loss had an objective response and PFS-6 in these patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss had an objective response; PFS-6 in these patients was 62%. This study indicates that ddTMZ is safe and effective in recurrent glioma, despite previous temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior efficacy of this schedule as compared to the standard day 1–5 every 4 weeks schedule.     

Efficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma

The current standard therapy for newly diagnosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m² for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1–14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8–4.2) and the median OS was 7 months (95% CI 5.1–8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7–32.2) and the 1-year OS rate was 12% (95% CI −1–25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3–4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high-grade glioma previously treated with temozolomide.     

Salvage chemotherapy with procarbazine and fotemustine combination in the treatment of temozolomide treated recurrent glioblastoma patients

The purpose of this study was to evaluate safety and efficacy of Procarbazine (PCB) and fotemustine (FTM) combination in the treatment of pre-temozolomide treated, recurrent GBM patients. The primary end-point was progression free survival at 6 months (PFS-6). Secondary end-points were overall survival, response rates (CR + PR) and toxicity. About 54 patients (41 men and 13 women) aged 26–68 years (median age, 53.5 years) with recurrent GBM were treated. PCB was administered as an oral dosage of 450 mg on days 1–2 and a total dose of 300 mg on day 3. FTM was administered on day 3, 3 h after the last PCB intake at a dose of 110 mg/mq/BSA. The treatment was repeated every 5 weeks. Treatment was continued for a maximum of six cycles or until disease progression. After two cycles of chemotherapy: 6 patients (11.2%) experienced a neuroradiographic partial response (PR), 29 patients (53.7%) had stable disease (SD), and 19 patients (35.1%) had progressive disease (PD). For the whole group of patients, the median PFS was 19.3 weeks (95% CI, 14.1–24.4 weeks), and PFS-6 was 26.7% (95% CI, 10.6–42.8%). Overall MST from the beginning of PCB + FTM chemotherapy was 28.7 weeks (95% CI, 24.8–32.7 weeks). At 6 and 12 months, 64.4% (95% CI, 51.5–77.3%) and 23.6% (95% CI, 10.1–37.1%) of patients were alive. The median survival time calculated from the first diagnosis was 20.8 months (95% CI, 16.7–24.8). We concluded that the PCB + FTM combination as done in the current trial for patients with recurrent GBM after treatment with TMZ showed some benefit with regards to increased survival and that a Phase III trial is warranted. Two errata are available for this article; the first one at , the second one at . An erratum to this article can be found at     

Radiopathological characteristics of cerebellar malignant glioma in adults

Our aim was to extract the radiopathological features of cerebellar malignant glioma in adults from the four cases we encountered. All four cases (two men and two women, aged 52–80 years; mean age, 67 years) had a floating sensation or vertigo at the onset of their disease. Initially, these patients were given a diagnosis of cerebellar infarction or cavernous angioma, or had faint abnormalities in the cerebellum that were overlooked. These patients were followed up for 2–14 months (mean, 6 months), and the tumor was detected when their clinical symptoms deteriorated. The tumor was located in the hemisphere in one patient and in the vermis in three patients. MRI revealed ring-like enhancement in two patients and nodular enhancement in two patients. All patients underwent subtotal tumor resection, followed by postoperative radiochemotherapy. However, three patients died at 16 to 44 months (mean, 28 months), and cerebrospinal fluid (CSF) dissemination was observed in three patients. Two cases were classified as WHO grade III and two as WHO grade IV. The pathological features were typical of malignant glioma, partially presenting the features of low-grade glioma, such as pilocytic, astrocytic, or oligodendroglial components. Nuclear pleomorphism and vascular endothelial proliferation were prominent, and micronecrosis was relatively less evident. The MIB-1 index was 12%–40%, and most of the patients were p53 protein positive. At the onset of cerebellar malignant glioma, diagnostic imaging shows few signs of brain tumor. Thereafter, tumors grow in a short period of time, following a rapid clinical course. Because cerebellar malignant glioma is a rare disease, it is difficult to differentiate it from metastatic brain tumors and primary central nervous system lymphoma by preoperative imaging. Some patho logical features suggesting malignant transformation from low-grade glioma were detected.     

Neurological outcome of long-term glioblastoma survivors

Extended survival of 3 or more years is rare in patients with glioblastoma (GBM) but is becoming more common. Clinical outcome has not been well studied. We reviewed GBM patients at Memorial Sloan-Kettering Cancer Center between 2001 and 2003 who were seen for two or more visits. Patient characteristics and long-term clinical outcomes were reviewed for patients who had survived 3 or more years following diagnosis. Thirty-nine (11%) of 352 GBM patients were identified as long-term survivors. Median survival was 9.15 years (range: 3–18 years). Median age was 47 years (range: 16–69); 13% were 65 years or older. Median KPS was 90 (range: 50–100). One long-term survivor underwent biopsy alone; 19 patients each had either complete or subtotal resection. All received focal radiotherapy (RT) with a median dose of 5940 cGy; 18% received concurrent temozolomide. Adjuvant chemotherapy was administered to 35 (90%). Twelve patients (31%) remained in continuous remission. Twenty-seven had tumor progression a median of 29.2 months after diagnosis (range: 1.2–167 months); 18 had multiple relapses. Median KPS at last follow-up was 70 (range: 40–100); 85% of long-term survivors had at least one significant neurologic deficit. Eleven (28%) had clinically significant RT-induced leukoencephalopathy, 9 (23%) developed RT necrosis and 9 (23%) treatment-related strokes. Treatment-related complications occurred a median of 2.7 years from diagnosis (range: 0.9–11.5 years). Long-term survivors remain rare, but are found across all age groups despite multiple recurrences; clinically significant delayed complications of treatment are common.     

High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.

PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.     

The efficiency of single agent docetaxel in patients with platinum-refractory non-small cell lung carcinoma

Summary   Background To evaluate the efficiency of docetaxel as second line chemotherapy in patients with platinum-refractory non-small cell lung carcinoma (NSCLC). Patients and methods Fifty-two patients with locally advanced or metastatic NSCLC who had platinum-refractory disease (progressed through or within 3 months of completion of first line therapy) and an Eastern Cooperative Oncology Group performance (ECOG) status 0–2 were treated with second-line chemotherapy consisting of single agent docetaxel (100 mg/m², intravenously, on day 1 of a 21-day cycle). The median number of treatment cycles was 4 (2–6). Disease-free (DFS) and overall survival (OS), response rates and toxicity were evaluated. Results The median progression-free survival of patients was 3 months (95% CI: 0.01–5.99) and overall survival was 7.2 months (95% CI: 2.2–9.5). One-year overall survival rate was 29%. Disease control (complete response, partial response, or stable disease) was achieved in 25 patients (48%) and overall response rate was 13% (7 patients). There were no complete responses. Seventeen patients (33%) had stable disease and twenty-seven patients (52%) had progressive disease. Age, gender, stage at diagnosis (IIIB vs. IV), performance status at initiation of second-line therapy (0–1 vs. 2) histopathological type (epidermoid vs. others), grade, LDH, albumin, weight loss were evaluated as prognostic factors; however, none of these had a significant affect on survivals. The protocol was well tolerated and there were no toxic deaths. Grade III–IV anemia was present in 8 patients (15%) and thrombopenia in 12 (23%) patients. The most frequent grade 3–4 toxicities were leucopenia (52%) and neutropenia (48%). Febril neutropenia occurred in 14 patients (26%). No patients experienced grade III–IV mucositis and diarrhea. Totally, the need of a dose reduction was about 25% and treatment delay (4–9 days) occurred in 5 patients (10%) and 7 patients (13%), respectively, because of toxicity. Conclusions Second-line chemotherapy with single-agent docetaxel offers a small but significant survival advantage with acceptable toxicity for patients with advanced NSCLC who have platinum-refractory disease.     

Phase II study of temozolomide in patients with relapsing high grade glioma and poor performance status

Temozolomide (SCHS2.365), an oral alkylating agent which penetrates the blood—brain barrier, evolved as an alternative to dacarbazine. The aim of this study was to evaluate the efficacy and safety of temozolomide in terms of overall survival, progression-free survival, clinical benefit and health related quality of life in symptomatic patients with relapsing malignant glioma and a poor performance status. Eleven patients were enrollel, in the study. The median age was 44.6 years. Patients were treated with temozolomide per os at a dose of 150–200 mg/m² daily for 5 consecutive days. Each cycle was repeated every 28 days. The median number of courses given per patient was 3.5. Nine patients were assessable for response. All patients were evaluable for toxicity. Based on radiographic findings 4 patients had stable disease (2 patients after a total of 16 cycles, and 2 patients after a total of 10 cycles). Four patients had progressive disease after 2 to 4 cycles. Of these 3 patients demonstrated a clinical benefit and one patient died after 3 cycles of treatment. Six patients had a significant clinical benefit even after 2 cycles of treatment with improvement of their neurological and performance status. Hematologic toxicity Gr II–III occurred in 3/9 patients. Nonhematologic toxicity consisted of Gr I nausea, and vomiting. In conclusion temozolomide appears to be a useful alternative for patients with relapsing malignant glioma after radiation and surgery and a poor performance status with little or no toxicity and considerable clinical benefit.     

Prognostic significance of the standardized uptake value of pre-therapeutic <Superscript>18</Superscript>F-FDG PET in patients with malignant lymphoma

Metabolic imaging with F-18-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography (PET) is widely used for staging and treatment evaluation of malignant lymphoma. To date, only a few studies have indicated that lower glucose metabolism measured by ¹⁸F-FDG PET before or early in the course of treatment of malignant lymphoma is associated with a favorable outcome. The aim of this study was to assess the prognostic capability of the ¹⁸F-FDG PET maximum standardized uptake value (SUV_max), a semiquantitative measurement of glucose metabolism, at the time of diagnosis of malignant lymphoma. We retrospectively analyzed data from 69 patients (median age: 61 and range 23–80) with malignant lymphoma (22 patients with Hodgkin’s disease [HD] and 47 patients with Non-Hodgkin’s lymphoma [NHL]) who had not received treatment before ¹⁸F-FDG PET imaging. Metabolic remission according to PET results was observed after chemotherapy in 50 patients (72.5%), while progressive disease or relapse was diagnosed in 19 patients (27.5%). Clinical follow-up revealed relapse in 4/50 patients with prior metabolic remission. A significantly lower (P < 0.01) baseline SUV_max level (median: 4.6 and range 1.5–12.9) was found in patients with subsequent metabolic and clinical response than in those with progressive or relapsing disease (median SUV_max 10.4, range 2.0–17.9). Thirty-seven of thirty-nine patients with baseline SUV_max < 7.4 achieved long-lasting remission after completion of chemotherapy (median follow-up: 28 months, range 4–112 months). Within this group with favorable outcome, there were no significant differences between SUV_max values in HD and NHL. A heterogeneous outcome was noted in 25 patients with a SUV_max ≥ 7.4 and ≤ 12.9 at diagnosis, with 16 patients experiencing disease progression or relapse and nine patients extended remission. The five patients with SUV_max > 12.9 showed disease progression at follow-up. Semiquantitative measurement of glucose metabolism (SUV_max) by ¹⁸F-FDG PET at diagnosis is a predictor of outcome of patients with malignant lymphoma.     

Phase II study of homoharringtonine in patients with recurrent primary malignant central nervous system tumors

A phase 11 trial of Homoharringtonine (HHT) was performed in 15 patients with recurrent or progressive malignant glioma. The drug was administered at a initial dose of 4 mg/m²/day by continuous 5 day intravenous infusion (3 mg/m²/day x 5 days for heavily pretreated patients). Courses were repeated every 3–4 weeks upon recovery from toxicity. No objective antitumor regressions occurred. Two patients had no change in their CT brain scans for 2–3 months and one patient had stable disease for 6 months. Toxicity was tolerable and included myelosuppression and occasionally mild hypotension. Chemosensitivity testing with HHT and several other chemotherapy drugs was performed in glioma cell lines, including cell lines derived from these patients. The results suggest that HHT is an inactive drug in malignant glioma using this dose schedule.     

Survival and quality of life after hypofractionated stereotactic radiotherapy for recurrent malignant glioma

Purpose To prospectively evaluate efficacy, side effects and quality of life in patients with recurrent malignant glioma after hypofractionated stereotactic radiotherapy. Methods and materials From 1/2003 to 8/2005, 15 patients with recurrent malignant glioma were prospectively scheduled for hfSRT with 5 × 7 Gy (90%-isodose). Median gross tumor volume and planning target volume were 5.75 (range, 0.77–21.94) and 22.4 (range, 4.22–86.79) cc, respectively. Irradiation was performed with the dedicated stereotactic radiosurgery system Novalis™ (BrainLAB, Heimstetten, Germany). Results Rates of remission, no change and progressive disease were 27%, 33%, and 40%, respectively, after a median follow-up of 9 months. Progression-free survival rates at 6 and 12 months were 75% and 53% respectively. Quality of life, measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire scores could be kept stable in two thirds of the patients for a median time of 9 months, respectively. Conclusion: Hypofractionated stereotactic radiotherapy with 5 × 7 Gy of recurrent high grade glioma is an effective treatment that helps to maintain quality of life for an acceptable period, comparable to the results obtained with current chemotherapy schedules. Combined approaches of radiotherapy, chemotherapy and other targeted therapies deserve further inverstigation.     

Carboplatin chemotherapy in patients with recurrent high-grade glioma

Aims

To investigate the efficacy of carboplatin chemotherapy in patients with recurrent high-grade glioma (HGG) who had received at least two previous lines of chemotherapy.

Materials and methods

Case notes of patients who had received chemotherapy with carboplatin for recurrent HGG between June 2005 and July 2008 were reviewed. Baseline characteristics and outcomes after treatment were recorded.

Results

Twenty-six patients received carboplatin as third- or fourth-line chemotherapy for recurrent HGG (grade III glioma n = 8; grade IV glioma n = 18). The median number of cycles completed was 2.5. The most common reasons for discontinuing treatment were progressive disease and death (n = 19; 73%). Three patients (12%) had a partial response, five (19%) had stable disease and 18 (69%) had progressive disease. Six month progression-free survival was 23% (25% in patients with grade III glioma and 22% in patients with grade IV glioma). The median time to disease progression from the first treatment with carboplatin was 9.0 weeks. The median survival was 19.4 weeks (27.9 weeks for patients with grade III glioma and 8.1 weeks for patients with grade IV glioma). Among patients with either stable disease or a partial response, the median survival was 42.4 weeks compared with 11.7 weeks in patients with progressive disease (hazard ratio for death with progressive disease on treatment: 5.02; 95% confidence interval 1.64-15.4; P = 0.005). Carboplatin was well tolerated overall.

Conclusions

Single-agent carboplatin has modest activity in patients with recurrent HGG who have received at least two lines of chemotherapy. The overall time to progression is short and over two-thirds of patients had to discontinue treatment due to progressive disease. Among the small proportion of patients achieving stable disease or a partial response to treatment, the median survival is improved. More effective but well tolerated regimens are required for this patient population.     

Neoplastic meningitis.

Neoplastic meningitis (NM) is a common problem in neuro-oncology occurring in approximately 5% of all patients with cancer, and is the third most common site of CNS metastases. NM is a disease affecting the entire neuraxis, and therefore clinical manifestations are pleomorphic affecting the spine, cranial nerves, and cerebral hemispheres. Because of craniospinal disease involvement, staging and treatment need to encompass all CSF compartments. Treatment of NM utilizes involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (ie, methotrexate, cytarabine, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of NM is palliative with an expected median patient survival of 2 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.     

High-grade astrocytoma treated concomitantly with estramustine and radiotherapy

Summary Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt®) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22–87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3–92.7) months for the radiotherapy only group and 17.3 (0.4–96.9+) months for the estramustine  + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1–89.2) and 10.3 (0.3–91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.     

Prospective assessment of activities of daily living using Modified Barthel’s Index in children and young adults with low-grade gliomas treated with stereotactic conformal radiotherapy

Purpose To report prospective evaluations of activities of daily living (ADL) in young patients with low-grade gliomas treated with stereotactic conformal radiotherapy (SCRT). Materials and methods Between April 2001 and February 2008, 38 children and young adults (age 5–25 years, median 12.5 years) with low-grade gliomas with residual/progressive disease and treated with SCRT were accrued in a prospective protocol. Patients underwent baseline and follow-up ADL assessments by the modified Barthel’s battery, which comprises domains of personal hygiene, bathing self, feeding, toilet, stair climbing, dressing, bowel control, bladder control, ambulation, and chair-bed transfer. Result The patient population consisted of 38 patients (male 29, female 9) with a diagnosis of residual or progressive low-grade glioma (pilocytic astrocytoma in 27, fibrillary astrocytoma in 5, ependymoma in 4, and oligodendroglioma and pleomorphic xanthoastrocytoma in 1 each). Three patients were visually handicapped. Mean of total modified Barthel’s ADL score (Barthel’ Index, BI) at baseline before staring SCRT was 94.5 (standard deviation 14.8, range 45–100). At 2-year and 3-year follow-up, mean BI was 97.1 and 99, respectively. At baseline pre-radiotherapy assessment, patients with impaired visual function and with low performance status (Karnofsky performance score, KPS < 70) had significantly lower BI than those with normal vision (P ≤ 0.001) and with good performance status (P = 0.001). On follow-up, maximum improvement in individual BI was seen in the ambulation-related domain in patients with impaired visual function (P = 0.027), low KPS (P = 0.015), and age less than 13 years (P = 0.103). The mean pre-radiotherapy baseline BI of three patients, who eventually developed local recurrence, was only 64 (SD 32.1) as compared with a baseline score of 97.18 seen in patients whose tumor remained controlled at follow-up (P ≤ 0.001). Conclusions Young patients with low-grade gliomas after surgical intervention had a lower than normal BI before starting radiotherapy, suggesting a decrease in ADL possibly due to tumor- and surgery-related factors. At 2-year and 3-year follow-up after SCRT, there was no further decrease in mean BI. A significant improvement in BI was seen in visually handicapped patients, patients with poor performance status, and younger patients. Patients who developed tumor recurrence at follow-up had a significantly lower BI at baseline than patients with controlled disease (P ≤ 0.001). Presented at the 39th Congress of the International Society of Pediatric Oncology, Mumbai, 1st–3rd November, 2007.     

Japanese Gastric Cancer Association Task Force for Research Promotion: clinical utility of <Superscript>18</Superscript>F-fluoro-2-deoxyglucose positron emission tomography in gastric cancer. A systematic review of the literature

Since April 2010, the Japanese Public Health Insurance System has covered the costs incurred for performing ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) imaging for patients with advanced gastric cancer. The aim of this review was to evaluate the clinical impact of PET for patients with gastric cancer. A systematic literature search was performed in PubMed/MEDLINE using the keywords “gastric cancer” and “PET” to search for relevant articles published from January 2000 to September 2010. The clinical impact of selected articles was assessed by the authors to evaluate the following: (a) tumor staging, (b) diagnosis for recurrent disease, (c) evaluation of treatment response, and (d) screening for gastric cancer. FDG uptake increases in papillary adenocarcinoma, tubular adenocarcinoma, and solid-type poorly differentiated adenocarcinoma. This uptake is also associated with glucose transporter 1 expression. The sensitivity and specificity of FDG-PET for metastatic lymph node detection were 21–40% and 89–100%, respectively. The sensitivity and specificity for distant metastasis detection were 35–74% and 74–99%, respectively. Treatment response can be detectable at an earlier stage by PET than by computed tomography (CT), because FDG uptake by cancer cells decreases according to the treatment response. In summary, although PET has limitations such as frequent false-negative cases in signet-ring cell carcinoma and non-solid type poorly differentiated carcinoma, it can contribute to the selection of a more appropriate treatment modality by detecting distant metastases and treatment response.