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L Specht

Publications and source records attributed to L Specht.

At least 19 recordsLinked to original sources
PubMed2006

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.

Combined Modality Therapy↗
PubMed2005

Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk.

BACKGROUND: Second malignancies (SM) are a major late effect of treatment for Hodgkin's disease (HD). Reliable comparisons of SM risk between alternative treatment strategies are lacking. OBJECTIVES: Radiotherapy (RT), chemotherapy (CT) and combined chemo-radiotherapy (CRT) for newly-diagnosed Hodgkin's disease are compared with respect to SM risk, overall (OS) and progression-free (PFS) survival. Further, involved-field (IF-)RT is compared to extended-field (EF-)RT. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, PubMed, EMBASE, CancerLit, LILACS, relevant conference proceedings, trials lists and publications. SELECTION CRITERIA: RCTs accruing 30+ patients and completing accrual before/during 2000, comparing at least two treatment modalities for newly-diagnosed HD. DATA COLLECTION AND ANALYSIS: Individual patient data were collected and assessed for data quality. Trialists submitted additional information concerning methods and data quality. Peto Odds Ratios (OR) with 95% confidence intervals (CI) were calculated for OS, PFS and SM-free survival. Secondary acute leukemia (AL), non-Hodgkin's lymphoma (NHL) and solid tumours (ST) were also analysed separately. MAIN RESULTS: 37 trials (9312 patients) were analysed: 15 (3343) for RT vs. CRT, 16 (2861) for CT vs. CRT, 3 (415) for RT vs. CT and 10 (3221) for IF-RT vs. EF-RT.CRT was superior to RT in terms of OS (OR=0.76, CI=0.66 to 0.89, p=0.0004), PFS (OR=0.49, CI=0.43 to 0.56, p<0.0001) and SM (OR=0.78. CI=0.62 to 0.98, p=0.03). The superiority of CRT also applied to early and advanced stages (mainly IIIA) separately. Excess SM with RT is due mainly to ST and is apparently caused by greater need for salvage therapy after RT.CRT was superior to CT in terms of PFS (OR=77, CI 0.68 to 0.77, p<0.0001). OS was better with CRT for early stages only (OR=0.62, CI 0.44 to 0.88, p=0.006). SM risk was higher with CRT (OR=1.38, CI 1.00 to 1.89, p=0.05), although not significant for early stages alone. This effect, also seen in AL and ST separately, was due directly to first-line treatment. Data were insufficient to compare RT to CT.EF-RT was superior to IF-RT (each additional to CT in most trials) in terms of PFS (OR=81, CI 0.68 to 0.95, p=0.009) but not OS. No significant difference in SM was observed. AUTHORS' CONCLUSIONS: CRT seems to be optimal for most early stage (I-II) HD patients. For advanced stages (III-IV), CRT better prevents progression/relapse but CT alone seems to cause less SM. RT alone gives a higher overall SM risk than CRT due to increased need for salvage therapy. Reduced SM risk after IF-RT instead of EF-RT could not be demonstrated. Due to the large number of studies excluded because no IPD were received, to the inclusion of many outdated treatments and to the limited amount of long-term data, one must be cautious in applying these results to current therapies.

Antineoplastic Agents↗
PubMed2000

Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck.

BACKGROUND: Results with docetaxel as single drug in squamous-cell head and neck cancer have been encouraging. The purpose of the present phase II study is to evaluate the antitumour efficacy and toxicity of the combination of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck (SCCHN) for whom no curative therapy is available. PATIENTS AND METHODS: Eligibility criteria included: written informed consent; WHO performance status < or = 2; age 18-70 years; adequate bone marrow, liver, and renal function; measurable or evaluable disease; no previous systemic chemotherapy (prior radiotherapy and/or surgery were allowed), no other previous or concurrent malignancy; no peripheral neuropathy. Treatment consisted of docetaxel 75 mg/m2 in a one-hour infusion after pre-treatment with prednisolone, followed by cisplatin 75 mg/m2 in a half-hour infusion preceded and followed by hydration. Treatment was repeated every three weeks for a maximum of eight cycles. RESULTS: Twenty-five patients (median age 52 years, range 33-66) entered the trial, all were evaluable for survival, twenty-four for response and toxicity. Twenty-four patients had undergone prior radiotherapy and seventeen had also had surgery. Nineteen had local-regional recurrence only, three had local-regional disease and distant metastases, and three had distant metastases only. Patients received a median of 5 treatment cycles (range 2-8). Overall response rate was 33% (8 of 24) of patients; complete response rate was 8% (2 of 24) of patients, lasting 2.2 and 17.1 months, respectively; partial response rate was 25% (6 of 24) of patients, lasting for a median of 4.9 months (range 1.7-11.6 months). Median survival was 11 months. Toxicity was relatively well tolerated. However, one patient died of probable toxicity (neutropenia and infection) and three patients discontinued treatment because of toxicity (massive oedema, myocardial infarction, persistent thrombocytopenia). The most frequent moderate-to-severe toxicity (75% of patients) was grade 3-4 neutropenia, transient in all but one patient. Grade 3 neuropathy occurred in one patient, none had grade 4. Grade 3 oral mucositis occurred in three patients, none had grade 4. Grade 2-3 hypomagnesaemia occurred in 10 patients requiring magnesium infusion. CONCLUSIONS: Docetaxel and cisplatin is an active combination in patients with recurrent or disseminated SCCHN. Remissions are however fairly short. Toxicity is significant, but generally manageable.

Adult↗
PubMed2000

Osteoradionecrosis of the jaws: clinical characteristics and relation to the field of irradiation.

PURPOSE: This study focuses on the clinical characteristics of patients with osteoradionecrosis (ORN) of the jaws and on the relation between the extent of the ORN and the field of irradiation. PATIENTS AND METHODS: The study group consisted of 80 patients referred for treatment of ORN. Charts of the extent of ORN, based on panoramic radiographs, were drawn by the clinical investigator and compared with charts of the field of irradiation drawn by the oncologists. Also recorded was diagnosis of the lesion, stage, location, treatment schedule, and period and dose of irradiation. Also documented were various potential initiating factors for ORN. RESULTS: Smoking habits of ORN patients were similar to those of other patients with head and neck cancer. A new primary tumor or a recurrence was diagnosed in 10% of the patients at the time of ORN. Only 3 patients had received accumulated doses of less than 60 Gy. More than half of the cases were initiated by removal of teeth; however, one third occurred spontaneously. ORN developed within the first 3 years in 74%; but ORN can emerge on a traumatic basis for an infinite number of years after radiation therapy. Widespread ORN may be symptomless apart from a discrete dehiscense of the oral mucosa. The predilection site for ORN is the mandibular molar region. All cases of ORN but 1 were found in the field of radiation. CONCLUSION: Because many ORN case are symptomless, more focus on mucosal dehiscence in the follow-up after radiation therapy is advocated in an effort to detect ORN at an early stage. The consequence of practically all ORN cases being located in the field of irradiation, together with tooth removal frequently being the initiating factor, should lead to a more aggressive preirradiation approach to dental pathology located within the field of radiation.

Adult↗
PubMed1998

A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85.

PURPOSE: A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx. PATIENTS AND TREATMENT: Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62-68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months. RESULTS: Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1-T2 48% versus T3-T4 36%, P = 0.0008), neck-nodes (N- 53% versus N+ 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P = 0.02) and sex (females 51% versus males 38%, P = 0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P = 0.002). A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P = 0.002). This trend was also found in the overall survival but to a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P = 0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38-2.45)), T3-T4 tumor (relative risk 1.65 (1.25-2.17)) and nimorazole (relative risk 0.69 (0.52-0.90)). The same parameters were also significantly related to the probability of dying from cancer. The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment. Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications. CONCLUSION: Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects.

Adult↗
PubMed1998

Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients. International Hodgkin's Disease Collaborative Group.

PURPOSE: To assess the effect of more extensive radiotherapy and of adjuvant combination chemotherapy on long-term outcome of early-stage Hodgkin's disease. METHODS: In a collaborative worldwide systematic overview, individual patient data were centrally reviewed on 1,974 patients in eight randomized trials of more versus less extensive radiotherapy and on 1,688 patients in 13 trials of radiotherapy plus chemotherapy versus radiotherapy alone. Crude mortality data on 226 patients in two other trials of chemotherapy were also reviewed. RESULTS: More extensive radiotherapy reduced the risk of treatment failure (resistant or recurrent disease) at 10 years by more than one third (31.3% v 43.4% failures; P < .00001), but there was no apparent improvement in overall 10-year survival (77.1 % v 77.0% alive). The addition of chemotherapy to radiotherapy halved the 10-year risk of failure (15.8% v 32.7%; P < .00001), with a small, nonsignificant improvement in survival (79.4% v 76.5% alive). This involved a reduction of borderline significance for deaths from Hodgkin's disease (12.3% v 15.4% dead at 10 years; P = .07), which was partly counterbalanced by a nonsignificant excess of deaths from other causes (12.4% v 10.0% 10-year risk). CONCLUSION: More extensive radiotherapy fields or the addition of chemotherapy to radiotherapy in the initial treatment of early-stage Hodgkin's disease had a large effect on disease control, but only a small effect on overall survival. Recurrences could be prevented by more extensive radiotherapy or by additional chemotherapy. However, if chemotherapy had not been given initially, recurrences were generally salvageable by re-treatment with chemotherapy. Hence, less intensive primary treatment--particularly a reduction in radiotherapy fields--appears to achieve similar survival rates as more intensive treatment, although more randomized evidence is needed to confirm this.

Antineoplastic Agents↗
PubMed1997

Infantile phosphofructokinase deficiency with arthrogryposis: clinical benefit of a ketogenic diet.

We report a 2-year-old boy with phosphofructokinase deficiency presenting in the newborn period with congenital arthrogryposis and severe myopathy, who has had significant improvement on a ketogenic diet since its institution at 4 months of age. We provide a rationale for use of this treatment and hypothesize it may be beneficial in other patients with phosphofructokinase deficiency and progressive muscular involvement. Confirmation awaits further clinical trials in carefully selected patients.

Arthrogryposis↗
PubMed1997

Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone.

To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse.

Adult↗
PubMed1996

Prognostic Factors in Hodgkin's Disease.

Prognostic factors in Hodgkin's disease (HD) are reviewed. The Ann Arbor staging classification remains the basis for evaluation of patients with HD. However, subgroups of patients with differing prognoses exist within the individual stages. In pathological stages I and II, the number of involved regions and the tumor mass in each region are important, and an estimate of the total tumor burden has proved significant. B symptoms, histological subtype, age, and gender are also generally significant but less important. Prognostic factors for laparotomy findings in clinical stages I and II are: number of involved regions, disease confined to upper cervical nodes, B symptoms, gender, histology, age, and mediastinal disease (variable influence). In clinical stages I and II, the same prognostic factors apply as for pathological stages I and II and for laparotomy findings, and also some indirect indicators of extent of disease such as erythrocyte sedimentation rate, anemia, and serum albumin. In advanced disease the number of involved nodal and extranodal regions, the total tumor burden, B symptoms, age, gender, histology, and a number of hematologic and biochemical indicators are significant. Research into serum values of certain HD-associated antigens and cytokines may in the future provide valuable tumor markers in HD.

Journal Article↗
PubMed1994

Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease.

PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681 patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology, presentation (supra- vs. infradiaphragmatic), number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, lactate dehydrogenase, alkaline phosphatase, serum albumin, and hemoglobin. RESULTS: Only age and histology showed significant prognostic impact in univariate and multivariate analyses. The influence of age may perhaps be attributed to suboptimal treatment of some older patients. Patients with nodal relapse had a better prognosis than patients with extranodal relapse, probably indicating that the latter had more extensive disease at relapse. The length of the initial disease-free interval had no influence on prognosis after relapse. CONCLUSION: The decisive factors for outcome after initial treatment with irradiation alone are a) the factors predicting the risk of relapse after initial radiotherapy and b) the factors predicting outcome after relapse, that is, histologic subtype and extent of disease at relapse.

Adult↗
PubMed1993

Surveillance following orchidectomy for stage I seminoma of the testis.

From 1985 to 1988, 261 unselected patients entered a nationwide Danish study of surveillance only for testicular seminoma stage I. The median follow-up time after orchidectomy was 48 months, range 6-67 months. 49 patients relapsed (19%). Sites of relapse were paraaortic lymph nodes in 41 patients, pelvic lymph nodes in 5, inguinal lymph nodes in 2 and lung metastases in 1 patient. The median time to relapse was 14 months, range 2-37 months. The 4-year relapse-free survival was 80%. 37 of the relapsing patients (76%) had radiotherapy as relapse treatment. Of these patients, 4 (11%) had a second relapse and received chemotherapy. 1 died of disseminated seminoma. Of the relapsing patients, 12 (24%) had chemotherapy as relapse treatment because of bulky (11 patients) or disseminated disease (1 patient). None of these patients have had a second relapse. However, 2 patients died of infection due to chemotherapy-induced neutropenia. Thus, there have been three seminoma-related deaths (1.1%). The testicular tumour size had an independent prognostic significance. The 4-year relapse-free survivals were 94, 82 and 64% for tumours < 3, 3 to < 6 and > or = 6 cm, respectively. Patients with tumours > or = 6 cm will now be given prophylactic radiation treatment, whereas we will continue to use surveillance only after orchidectomy for patients with tumours < 6 cm.

Adult↗
PubMed1992

Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach.

We studied 27 Duchenne muscular dystrophy patients having spinal fusion for scoliosis. One patient died intraoperatively of cardiac arrest; all others have done well with no instances of malignant hyperthermia, postoperative ventilatory system dependence, pneumothorax, persisting infection, neurologic damage, nonunion, or pain. The anesthetic management included primarily intravenous general anesthetics with minimal myocardial depressant effects, avoiding succinylcholine and inhalation agents. Preoperative cardiac studies aided anesthetic management intra-operatively. There was an almost universal sinus tachycardia. Holter monitoring defined 4 of 16 with ventricular premature beats, 4 of 16 with atrial premature beats, and no ventricular tachycardia or atrial flutter or fibrillation. Echocardiogram demonstrated mitral prolapse in 2 of 22, frequent abnormal systolic performance with abnormal shortening fraction less than 28% in 7 of 16, and reduced rate-corrected velocity of fiber shortening in 9 of 15. Afterload was elevated in 7 of 15. The mean forced vital capacity (FVC) preoperatively was 45.3 +/- 15.9% with continuing diminution to 28.7 +/- 14.9% at 3.3 +/- 2.2 years after surgery. The main benefit of surgical stabilization is the relative ease and comfort of wheelchair seating compared with those nonoperated patients who develop progressive deformity. We have not seen lasting improvement or stabilization in FVC following surgery as decreasing function is related primarily to muscle weakness.

Adolescent↗