Prognostic Groups Of Patients Research Articles

A Long-Term Follow-Up Study after Split-Course Irradiation with Concurrent Chemotherapy (Carboplatin) for Locally Advanced Head and Neck Cancer and a Review of the Literature

Background: Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. The purpose of this study was to evaluate the efficacy and toxicity of split-course radiotherapy combined with concurrent carboplatin chemotherapy after long-term follow-up. Patients and Methods: From August 1987 to May 1994, 66 patients (54 males, 12 females, mean age 58 years) with advanced inoperable oropharynx cancer were treated at the University of Göttingen, Göttingen, Germany. Tumour localization in the oropharynx was: tonsil (n = 33), base of tongue (n = 28), soft palate (n = 2) and posterior pharyngeal wall (n = 3). Forty-nine patients presented with a T₄ tumour, 15 were T₃ and 2 were T₂. The nodal status was distributed as follows: N0 (n = 7), N1 (n = 5), N2 (n = 28) and N3 (n = 26). A total radiation dose of 5,670 cGy was applied in 6 weeks as a split-course regimen (2 × 2.1 Gy/day, 4 times a week, weeks 1 and 2 and weeks 5 and 6). Concomitant carboplatin chemotherapy was given each radiotherapy day before irradiation (50 mg/m²). Results: In December 2003, 12 patients were still alive. Survivors have reached a maximum follow-up of 170.5 months (median 14.3 months). Two- and 5-year overall survival was 32 and 18%, 2-year disease-free survival 27%. Therapy was tolerated moderately (19% grade 3 skin reaction, 26% grade 3 mucositis, 23% grade 3 xerostomia, 20% grade 3 leucopenia, 8% grade 3 thrombopenia and 25% grade 3 anaemia). Conclusion: Split-course radiotherapy and concomitant carboplatin chemotherapy can be carried out in inoperable head and neck cancer without severe toxicity. After long-term follow-up, survival rates are unfavourable in this poor prognostic group of patients.

Favorable Survival of Multiple Myeloma Patients with t(11;14)(q13;q32) Plus Normal Chromosome 13q.

Previous studies have shown that specific chromosomal abnormalities are of major prognostic significance in patients with multiple myeloma (MM). It has been recently suggested that a t(11;14)(q13;q32) may be an indicator of favorable outcome in MM. In this investigation, we analyzed 163 patients with newly diagnosed MM (53% treated by high-dose therapy) to address the question whether or not the simultaneous occurrence of a t(11;14) and a deletion 13q [del(13q)], an established negative prognostic factor in MM, has any impact on prognosis. DNA-specific probes for IgH (14q32) and cyclin-D1 (11q13) were used for interphase FISH analysis of clonal plasma cells (cytoplasmic Ig positive). A t(11;14) by FISH was shown in 27 of the 163 MM patients (16.6%); the abnormality was present in the majority (median, 89%) of clonal plasma cells. Immunohistochemical analysis of CYCLIN-D1 expression was carried out in 72 patients, of whom 11 had a t(11;14) by FISH; all 11 patients had evidence for CYCLIN-D1 protein expression. Presence of a t(11;14) did not show significant correlations with standard laboratory and clinical MM features including type of the paraprotein, hemoglobin, creatinine, LDH, albumine, calcium, CRP, and beta-2-microglobulin (b2M). In contrast to a recent report, there was also no association with CD20 expression by MM cells. With respect to survival, presence of any 14q-translocation (52% of patients) was associated with similar overall survival times (OS) compared to patients lacking a t(14q), whereas patients with a t(11;14) experienced prolonged OS (median, 70+ months vs. 59.8 months among patients without t(11;14); P = .071). This survival advantage was even greater among the 16 patients with t(11;14) who were also normal for 13q (P = .02); however, occurrence of a del(13q) concomitantly with a t(11;14) was indicative for shortened progression-free survial (17.7 months vs. 31.6 months; P = .17) and OS (P = .07). A survival benefit of MM patients with a t(11;14) was particularly evident for the population receiving standard-dose chemotherapy (median OS not yet reached; P = .02). By multivariate Cox regression analysis, low serum b2M at diagnosis (P = .001), absence of a del(13q) (P = .004), high-dose therapy (P = .034), and presence of t(11;14)/no del(13q) (P = .069) emerged as independent favorable parameters for OS. Thus, according to the cytogenetic pattern, three prognostic groups of patients could be discriminated (P < .001): patients with good [t(11;14), no del(13q)], intermediate [no t(11;14), no del(13q)], and poor prognosis [no t(11;14), del(13q)]. We conclude that MM with t(11;14) represents a heterogenous entity, and only the cytogenetic pattern t(11;14)/no del(13q) characterizes the most favorable prognostic group of MM, with sensitive disease to multiple lines of anti-MM therapy.

Pour améliorer le pronostic des gliomes

We report the palliative effectiveness of a hypofractionated radiotherapy regimen in patients with poor prognosis high grade glioma. Thirty-eight elderly, and/or disabled patients received radiotherapy to a dose of 30 Gy in 6 fractions over 2 weeks to a planning target volume defined by the enhancing tumour and a 2-cm margin. The median survival was 6 months with a 1-year survival rate of 23%. Treatment was without acute toxicity. One month after radiotherapy, functional status, assessed using a verbally administered Barthel index, improved in 38% and remained stable in a further 39% of surviving patients. At 3 months 39% of surviving patients had improved and a further 12% remained stable. We conclude that in the poor prognostic group of patients with high grade glioma hypofractionated partial brain radiotherapy is well tolerated, convenient and provides effective palliation in a proportion of patients. Comparison with conventional radiotherapy or symptomatic care alone require further evaluation in randomised studies.

Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia: results in patients treated in second molecular remission or with molecularly persistent disease.

In all, 17 consecutive patients in hematological complete remission (HCR) of acute promyelocytic leukemia (APL) received allogeneic stem cell transplantation (SCT) from an HLA-identical sibling and were monitored by reverse transcriptase polymerase chain reaction of PML/RARalpha prior and after transplant. Median age was 31 years (range 3-50 years). At 10 years, the actuarial probabilities of nonrelapse mortality, relapse and disease-free survival were 32% (95% CI: 8-56%), 33% (95% CI: 6-60%) and 46% (95% CI: 22-70%). Six patients tested PCR +ve (1st HCR n=2; 2nd HCR n=3; 3rd HCR n=1) and 11 PCR -ve (2nd HCR n=11) pre-SCT. Of the six patients PCR +ve, two showed early persistence of PCR positivity and converted to sustained PCR negativity after CSA withdrawal (one died of secondary tumor in molecular remission and one is alive in relapse), while four converted to PCR -ve rapidly (one died of the underlying disease and three are in molecular remission). Of the 11 patients PCR -ve pre-SCT, six died (four of transplant-related mortality, one of relapse and one after heart transplantation) and five are alive, four in molecular remission and one is in relapse. Allogeneic SCT seems a valid option for advanced APL, particularly for the poor prognostic group of patients with pre-SCT molecularly persistent disease.

Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score).

A clinical staging system for cancer patients provides guidance for patient assessment and making therapeutic decisions. It is useful in deciding whether to treat a patient aggressively, and in avoiding the overtreatment of patients who would not tolerate the treatment or patients whose life expectancy rules out any chance of treatment. Clinical staging is also an essential tool for comparison between groups in therapeutic trials and for comparison between different studies. The current classifications most commonly used for hepatocellular carcinoma (HCC) are the Okuda stages, the Child-Pugh staging system, tumor node metastasis (TNM) staging, and the Cancer of the Liver Italian Program (CLIP) score. Among these, the CLIP score is currently the most commonly used integrated staging score, including both tumor stage and liver disease stage. Although the CLIP score has been well validated by many authors in terms of its prognostic value in HCC patients, this score has some problems and limitations when applied to currently diagnosed HCC patients, who are diagnosed in the early stage of disease. First, the CLIP score can discriminate score 0- to 3-patient populations, but it is not able to discriminate score 4- to 6-patient groups. Second, the definition of tumor morphology in the best prognostic group is too advanced, i.e., uninodular and a tumor extent of less than 50% of the liver. As a result, the prognosis of the CLIP system best prognostic group is not so good. In other words, this system cannot identify the best prognostic group who would benefit from curative and aggressive treatment. Third, nearly 80% of the patient population is classified as having a CLIP score of 0-2, as confirmed by many studies, which shows poor stratification ability. In contrast, a new staging system based on the Liver Cancer Study Group of Japan (LCSGJ), the Japan Integrated Staging (JIS) score is currently proposed in Japan. This staging system combines Child-Pugh grade (grade A, score 0; grade B, score 1; grade C, score 2) and TNM staging by the LCSGJ criteria (stage I, score 0; stage II, score 1; stage III, score 2; stage IV, score 3). The stratification ability of the JIS scoring system is much better than that of the CLIP scoring system. The JIS scoring system also performed better than the CLIP scoring system in selecting the best prognostic patient group. The cumulative 10-year survival rates of the best prognostic groups in the CLIP staging system (CLIP score 0) and JIS staging system (JIS score 0) were 23% and 65%, respectively (P < 0.01). All scoring systems arise as a compromise between simplicity and discriminatory ability. We confirmed that the JIS score increases predictive efficacy, while remaining simple compared with the CLIP score. Because the JIS score is quite easily obtained and is objective, we strongly propose it for widespread use as a prognostic staging system for HCC in clinical practice.

Role of endocavitary brachytherapy with or without chemotherapy in cancer of the nasopharynx

Purpose : We previously reported our preliminary experience with nasopharyngeal cancer boosted after 60–70 Gy external beam radiotherapy (EBRT) by fractionated endocavitary brachytherapy (ECBT) to cumulative doses of 78–82 Gy. As for Stage III–IVB disease, cisplatin (CDDP)-based neoadjuvant chemotherapy (CHT) was given. The aim of the present study was to define the role of ECBT more accurately. Methods and Materials : Ninety-one patients with primary nasopharyngeal cancer, staged according to the 1997 UICC/AJCC classification system, were treated between 1991 and 2000 with 60–70 Gy external beam radiotherapy and 11–18 Gy ECBT. Of the 91 patients, 21 were treated in conjunction with CHT and 70 without CHT. Tumors were subdivided into undifferentiated (UD) and well, moderately, and poorly differentiated (WMP-D) subtypes. Treatment results were analyzed for local control (LC), disease-free survival (DFS), freedom from distant metastasis, and overall survival (OS). Results : A univariate and multivariate Cox regression analysis found stage, treatment period, age, and grade significant for LC, DFS, and OS. At 2 years, for Stage I–IIB (1st period, 1991–1996), the LC, DFS, and OS were 96%, 88%, and 80%, respectively, vs. 65%, 46%, and 52% for Stage III–IVB. For the 2nd treatment period (1996–2000; CHT for Stage III–IVB), the LC, DFS, and OS at 2 years was 100%, 90%, and 61% (Stage I–IIB), respectively, vs. 86%, 74%, and 66% (Stage III–IVB). Three prognostic groups (PGs) were constructed. For the 1991–1996 period, at 2 years, patients in the good PG (UD Stage I–IIB disease) had 100% LC and 92% OS; those in the intermediate PG (UD Stage III–IVB or WMP-D Stage I–IIB), had 94% LC and 71% OS; and those in the poor PG (WMP-D Stage III–IVB) had 47% LC and 40% OS. For the 1996–2000 period, at 2 years, the good PG had 100% LC and 88% OS; the intermediate PG had 100% LC and 64% OS; and the poor PG had 71% LC and 60% OS. Conclusion : For Stage I–IIB disease treated between 1991 and 2000, at 3 years, the LC and OS was 97% and 67%, respectively. The results with 77–81 Gy without CHT warrant EBRT combined with ECBT to remain our standard of care for Stage I–IIB disease. For N2-3 and/or T3-4 tumors, in addition to high doses of RT, neoadjuvant CHT was administered as of 1996. For the 1991–2000 period, at 3 years, the LC was 86% and the OS was 72% with CHT, with little extra morbidity; they were 68% and 35% without CHT. Because of better target coverage and sparing, T3-4 tumors are currently boosted by stereotactic RT to 81.2 Gy.

Nonsevere community-acquired pneumonia: correlation between cause and severity or comorbidity.

Community-acquired pneumonia frequently constitutes a nonsevere infection manageable at home. However, for these low-risk episodes, the epidemiological features have not been carefully analyzed. To determine the cause of nonsevere community-acquired pneumonia and to investigate if a correlation exists between cause and severity or comorbidity. During a 3-year period, all patients with nonsevere community-acquired pneumonia, according to the Pneumonia Patient Outcome Research Team prognostic classification (patients in groups 1-3), were included in the study. Causes were investigated through the following procedures: cultures of blood, sputum, and pleural fluid; serologic tests; and polymerase chain reaction methods to detect Streptococcus pneumoniae DNA in whole blood or Mycoplasma pneumoniae and Chlamydia pneumoniae DNA in throat swab specimens. Of 317 initially included patients, 247 were eligible for the study. A microbial diagnosis was obtained in 162 patients (66%), and the main pathogens detected were S pneumoniae (69 patients [28%]), M pneumoniae (40 patients [16%]), and C pneumoniae (28 patients [11%]). For the 58 patients in prognostic group 1, M pneumoniae was the most prevalent cause, and atypical microorganisms constituted 40 (69%) of the isolated agents. In contrast, for patients in prognostic groups 2 and 3, S pneumoniae was the leading agent, and a significant reduction of M pneumoniae cases and a greater presence of other more uncommon pathogens were observed. The existence of comorbid conditions was not a determining factor for particular causes. Among low-risk patients with community-acquired pneumonia, there was a certain correlation between severity and cause. In contrast, the existence of a comorbidity did not have a predictive causative value.

A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma.

Optimal histologic criteria for the classification of and grading of ependymomas, including their anaplastic forms, remain elusive. This is especially true because of the poor correlation of these criteria with clinical outcome. The aim of this study was to identify the histopathologic parameters that could distinguish different prognostic groups of patients with ependymomas. Eighty-one patients with ependymal tumors, including those originally diagnosed ependymomas, anaplastic ependymomas and myxopapillary ependymomas, were enrolled in this study. Thirteen histologic parameters, including hypercellularity, nuclear pleomorphism, mitoses, endothelial proliferation, necrosis, clear cell, thrombi, dystrophic calcification, psammoma bodies, bone, cartilage, Rosenthal fibers and MIB-1 labeling index (LI), were evaluated in each patient and correlated with clinical outcome. We assigned one score for each histopathologic parameter evaluated and used a stepwise selection method with entry model based on the significance of the log-rank statistic to formulate a scoring model. Four parameters were chosen in this process, including mitoses > or = 4/10 hpf (1.7/mm2), hypercellularity, endothelial proliferation and necrosis. The sum of these four parameters (scores) was the histopathologic score of the tumor. The progression-free survival (PFS) and overall survival (OS) of patients with histopathologic scores 0 and 1 were significantly better than those with histopathologic scores 2, 3 and 4 (p < 0.001 and p = 0.005, respectively). Because of the latter finding, we proposed that anaplastic ependymoma could be diagnosed by the presence of any two of the aforementioned four parameters. Multivariate analyses including clinical and histopathologic variables showed that histopathologic score > or = 2 and subtotal resection were the factors related to increased risk of recurrence, while histopathologic score > or = 2 was the only factor related to overall survival. Based on the above findings, we concluded that histopathology is an important prognostic indicator for patients with ependymomas.

VEGF-B expression in human primary breast cancers is associated with lymph node metastasis but not angiogenesis.

Angiogenesis is essential for tumour growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently VEGF-B, a new VEGF family member that binds to the tyrosine kinase receptor flt-1, has been identified. Although the importance of VEGF has been shown in many human tumour types, the contribution of VEGF-B to tumour neovascularization is unknown in any tumour type. This study therefore measured the mRNA level of VEGF-B and its receptor flt-1 by ribonuclease protection assay and the pattern of VEGF-B expression by immunohistochemistry in 13 normal breast samples and 68 invasive breast cancers. Flt-1 expression was significantly higher in tumours than in normal breast (p=0.02) but no significant difference was seen in VEGF-B between normal and neoplastic breast (p=0.3). There was a significant association between VEGF-B and node status (p=0.02) and the number of involved nodes (p=0.01), but not with age (p=0.7), size (p=0.6), oestrogen receptor (ER) (p=0.2), grade (p=0.5) or vascular invasion (p=0.16). No significant relationship was present between VEGF-B and flt-1 (p=0.2) or tumour vascularity (p=0.4). VEGF-B was expressed mostly in the cytoplasm of tumour cells, although occasional stromal components including fibroblasts and endothelial cells were also positive. No difference in VEGF-B expression was observed adjacent to regions of necrosis, in keeping with this VEGF family member not being hypoxically regulated. These findings suggest that VEGF-B may contribute to tumour progression by a non-angiogenic mechanism, possibly by increasing plasminogen activators and hence metastasis, as has been described in vitro. Measurement of VEGF-B together with other angiogenic factors may identify a poor prognostic patient group, which may benefit from anti-VEGF receptor therapy targeted to flt-1 (VEGFR1) as well as kdr (VEGFR2).

Identification of prognostic subgroups among patients with metastatic ‘IGCCCG poor-prognosis’ germ-cell cancer: An explorative analysis using cart modeling

The IGCCCG classification has identified three prognostic groups of patients with metastatic germ-cell tumors. 'Poor prognosis' is based on primary tumor localization, the presence of visceral metastases, and/or high tumor-marker levels. The overall survival rate of these patients is about 45%-55%. The present analysis attempts to identify subsets of patients with a more or less favorable outcome among the 'poor-prognosis' group. We retrospectively explored prognostic subgroups in 332 patients with 'IGCCCG' poor-risk GCT using the classification-and-regression-tree model (CART). The following variables were included: primary tumor localization, presence of visceral or lung metastases, presence of an abdominal tumor, number of metastatic sites, serum levels of beta-HCG, AFP and LDH. All patients had been treated with cisplatin-etoposide-based chemotherapy within controlled clinical trials between 1984 and 1997. gonadal/retroperitoneal (G/R) primary tumor 260 patients (78%), mediastinal primary tumor 72 patients (22%), visceral metastases 205 patients (62%) including 33 patients with CNS metastases, lung metastases 247 patients (74%), abdominal tumor 241 patients (72%), elevated AFP, beta-HCG or LDH levels 235 (71%), 253 (76%) and 275 (83%) of patients, respectively. Patients with primary mediastinal disease plus lung metastases exhibited the worst two-year PFS (28%), whereas patients with a primary G/R tumor and without visceral metastases showed the highest chance of two-year PFS (75%). The latter group of patients without visceral metastases and with a primary G/R tumor also had the most favourable two-year OS (84%). In contrast, patients with a primary mediastinal tumor and visceral metastases displayed the worst two-year OS (49%). Different prognostic subsets of patients can be identified among the group of 'poor-prognosis' GCT patients. The CART analysis model results in a hierarchy of prognostic factors which may allow to more precisely estimate the individual patient's prognosis. Identifying subgroups of 'very poor-prognosis' among 'poor-prognosis' patients may allow to test for new treatment strategies in selected subgroups.

Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma

A new, internationally accepted histologic classification of renal cell carcinoma (RCC) and a new edition of the TNM staging system were introduced in 1997. In the latter, there was a dramatic change in the pT classification of organ-confined renal cancer in which the break point between category pT1 and pT2 was increased from 2.5 cm to 7 cm. To study the significance of the new pT classification and the new recommendations for histologic classification, 588 nephrectomy specimens were reevaluated to define morphologic prognostic parameters in RCC. pT classification (TNM 1997), histologic subtype, histologic tumor grade, presence of necrosis, and sarcomatoid differentiation were assessed. The histopathologic review according to the new classification revealed 487 conventional (clear cell) (83%), 64 papillary (11%), 31 chromophobe (5%), and 6 collecting duct (1%) RCCs. Clinical follow-up was available for 470 RCCs. The new pT classification (1997) was strongly correlated with patient survival (P < 0.0001). Histologic grade, presence of necrosis, and sarcomatoid differentiation provided independent prognostic information on the clear cell subtype of renal cancer. Sarcomatoid differentiation, but not tumor necrosis, portended a dismal prognosis for patients with papillary RCC. Chromophobe RCC was associated with a significantly better prognosis than clear cell RCC (P = 0.05). Papillary RCC with scanty cytoplasm and small cells (type 1) behaved less aggressively than papillary tumors with eosinophilic cytoplasm and large cells (type 2; P < 0.001). Accurate histologic classification according to the new recommendations has implications because the prognostic importance of other histologic features that are of independent significance varies with tumor subtype. The data suggest that the new pT classification allows good separation of prognostic groups of patients with renal cancer.

Mitoxantrone-DHAP with GM-CSF: An Active but Myelosuppressive Salvage Therapy for Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma

This study was designed to evaluate the efficacy and toxicity of dose intensifying DHAP (dexmethasone, cytarabine and cisplatin) salvage chemotherapy by adding mitoxantrone with GM-GSF support in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). From March 1992 to January 1995, 22 patients with intermediate and high grade (aggressive) NHL refractory or relapsed after adriamycin containing chemotherapy regimens were treated with M-DHAP+GM-CSF, (dexamethasone 40 mg IV days 1–4, cisplatin 100 mg/m2 IV by continuous infusion over 24 hours on day 1, cytarabine 2 gm/m2, IV every 12 hours for 2 doses on day 2, mitoxantrone 10 mg/m2 IV on days 3 and 4 and GM-CSF 250–500 μg/m2 SC daily beginning day 5 until absolute neutrophil count recovery. Most patients had poor prognostic factors including primary refractory disease (18/22), bulky disease (12/22), elevated LDH (9/22), or bone marrow involvement (8/22). All 22 patients were evaluable. The overall response rate was 41% (CR 23% and PR 18%). There were three toxic deaths, all related to sepsis. Median progression free survival (PFS) and overall survival (OS) rates were 5.2 months and 11.8 months respectively. At the same time of the analysis two patients were alive after high-dose therapy and bone marrow transplant at 34 and 36 months follow-up and two were alive with disease. The maximal acceptable dosage of mitoxantrone was 10 mg/m2 × 2 due to serious hematologic toxicity. Treatment delays and dose reductions compromised delivering the optimal dose intensity of M-DHAP. A poor prognostic group of patients with refractory or recurrent aggressive lymphoma, many of whom were not eligible for high-dose therapy and stem cell transplantation were treated with repeated cycles of dose intensified DHAP with growth factor support. Although M-DHAP had therapeutic activity even in patients considered to have primary refractory disease, myelosuppression was dose limiting and frequently limited the number of cycles. Therefore, if M-DHAP is to be further evaluated, therapeutic results may be improved further by incorporating strategies to reduce myelotoxicity such as the use of growth factors to reduce platelet transfusion requirements or the use of autologous stem cell support after each cycle.

A prospective phase ii trial of concomitant chemotherapy and radiotherapy with delayed accelerated fractionation in unresectable tumors of the head and neck

Background Our study is a prospective evaluation of unresectable malignant cancers of the head and neck treated with concomitant chemotherapy and radiotherapy (RT) using delayed accelerated fractionation (concomitant boost). Methods Between January 1988 and March 1995, 82 patients with unresectable cancers of the head and neck were enrolled in this phase II study. Of these, 52 patients were treated and followed for a minimum of 3 years and are the subject of this analysis. All patients had T4 lesions and were stage IV according to the American Joint Committee on Staging Criteria (AJCC). Patients received RT with accelerated fractionation to a total of 70 Gy in 6 weeks using a concomitant-boost technique. Concomitant cis platin (100 mg/M2) was given on days 1 and 22 of RT. Twenty-seven patients received mitomycin-C (7.5 mg/M2) on days 1 and 22, and 1 patient received mitomycin-C on day 1. In addition, 27 patients received adjuvant chemotherapy with cis platin and vinblastine. The mean follow-up was 45 months (range, 36–72 months). The minimum follow-up for surviving patients is 3 years. Results At 3 years, the local control rate was 58%. Three-year local control rates for paranasal sinus, nasopharynx, oropharynx, and larynx/hypopharynx were 78%, 78%, 64%, and 100%, respectively. For all patients, the distant-metastasis-free survival was 56%, and the overall survival rate was 36%. Patients with oral cavity cancers experienced worse overall survival versus other sites, 0% versus 47% (p = .03). Salivary cancers also showed worse survival versus other sites, 0% versus 47%, but was not statistically significant. Severe acute complications occurred in 34% of patients. Treatment-related toxicity also resulted in the death of 2 patients. Severe late complications occurred in 7% of patients. Conclusions Treatment of this poor prognostic group of patients with aggressive chemotherapy and RT produced surprisingly good local control and survival. © 1998 John Wiley & Sons, Inc. Head Neck 20: 497–503, 1998.

MIB-1 labeling index in nonpilocytic astrocytoma of childhood: a study of 101 cases.

The prognosis of pediatric patients with nonpilocytic astrocytoma, and in particular those with anaplastic astrocytoma, is somewhat unpredictable. This study used MIB-1 monoclonal antibody, a proliferative marker that can be used in formalin fixed paraffin embedded tissues, to study nonpilocytic pediatric astrocytoma. Astrocytoma, anaplastic astrocytoma, and glioblastoma specimens excised from a total of 101 pediatric patients during the period from January 1975 to September 1996 were retrieved from the authors' surgical pathology file. Histologic grading of the specimens was performed based on a modified Ringertz system. The proliferative potential of the tumors was estimated by using the MIB-1 labeling index (LI), which was evaluated with morphologic grades of tumors and survival of the patients. Of the 101 patients, 34 had astrocytoma, 33 had anaplastic astrocytoma, and 34 had glioblastoma. Their mean survival times were 165.2+/-14.9 months (mean+/-standard error; SE), 46.1+/-9.9 months, and 21.8+/-5.6 months, respectively. The mean MIB-1 LI of different tumor grades were as follows: astrocytoma, 3.9+/-4.3 (mean+/-standard deviation; range, 0.0-21.6); anaplastic astrocytoma, 24.3+/-15.6 (range, 1.7-62.8); and glioblastoma, 35.9+/-16.4 (range, 7.36-63.3). The mean survival of the entire group of patients with LIs < or = 11 was 173.2+/-12.2 months (mean+/-SE), and the mean survival of those with LIs > 11 was 20.3+/-4.1 months. The survival of anaplastic astrocytoma patients with LIs < or = 11 was similar to that of astrocytoma patients, whereas the survival of anaplastic astrocytoma patients with LI > 11 was similar to that of patients with glioblastoma. The results of the current study show that histopathologic grading can predict the outcome for patients with astrocytomas and glioblastomas, whereas MIB-1 LI can separate better and worse prognostic groups in patients with anaplastic astrocytoma.

Relationship between DNA Ploidy and Functional Estrogen Receptors in Operable Prostate Cancer

To evaluate the relationship between the nuclear DNA content and the tissue estrogen receptor (ER) level in patients with operable adenocarcinoma of the prostate. Surgical specimens taken from 73 patients with clinically localized prostate cancer were studied. Tumor DNA ploidy pattern as measured by flow cytometry was correlated with the level of functional ER using the nuclear biopsy assay. Forty-five percent of the tumors were DNA diploid, and 55% had an abnormal ploidy pattern (DNA tetraploid or DNA aneuploid). The ER level ranged from 0 to 6,475 fmol/mg DNA (mean 839 fmol/mg DNA). Twenty-two percent had no functional receptors. Marked association was noted between ER and nuclear DNA content. Seventy-five percent of the tumors with no ER had abnormal ploidy patterns. The mean receptor level for DNA diploid prostate cancer was 1,034 fmol/mg DNA versus 661 fmol/mg DNA for DNA nondiploid tumors (p < 0.008). An inverse correlation was found between ER values and histologic grade or pathologic stage. High-grade and high-stage tumors had lower levels of ER compared to low-grade and early-stage carcinomas. Our results demonstrate an association between ER values and variables that predict prognosis in prostate cancer. It is possible that this parameter may be helpful in identification of prognostic groups in patients with prostate cancer.

Identification of intermediate-risk prostate cancer patients treated with radical radiotherapy suitable for neoadjuvant hormone studies

We undertook a retrospective review of patients presenting with apparently localised prostatic carcinoma to a single practitioner for consideration of radiation therapy to clarify the characteristics of those patients who might benefit from the use of neo-adjuvant androgen deprivation. Of 133 patients referred between January 1989 and June 1994, 85 were considered suitable for radical therapy, of whom 31 were treated with hormone therapy prior to radiotherapy, frequently on the basis of an elevated PSA. Increasing PSA levels ( p = 0.0016) and Gleason grade ( p = 0.026) were independent variables for relapse. It was possible to define three prognostic groups of patients, on the basis of initial PSA and Gleason grade. Those of intermediate risk (PSA < 10 μg/l, Gleason score 8–10; PSA 10–25 μg/l, Gleason 5–7 or 8–10; PSA > 25 μg/l, Gleason score 2–4) had a superior duration of disease-free survival if given initial hormone therapy. This group of patients is potentially the most likely to benefit from such an approach and should be enrolled in prospective randomised studies of neoadjuvant androgen deprivation.

Prediction of permanent work disability in a follow-up study of early rheumatoid arthritis: results of a tree structured analysis using RECPAM.

The objectives of this study are: (a) to determine the occurrence of permanent work disability (PWD) in early rheumatoid arthritis (RA); (b) to identify prognostic groups of patients; (c) to assess the employment rates for these groups over time. Seventy-three gainfully employed consecutive out-patients with early RA (> or = 5 ARA 1958 criteria, disease duration < or = 12 months) at time one (T1) were re-examined at time two (T2) after a mean follow-up of 6 yr (S.D. +/- 2 yr). Potential risk factors, identified at T1, for PWD at T2 were entered in a tree structured survival analysis using RECPAM (RECursive Partition and AMalgamation). Cumulative 3 yr employment rates (3-yrER +/- S.E.M.) were computed from the resulting Kaplan-Meier curves. At T2, PWD occurred in 27 of the 73 patients (37%). The fastest decline in the employment rate was found within the first 3 yr of the disease onset, with a 3-yrER reduced to 73 +/- 5%. The group with the poorest prognosis (n = 14; 3-yrER 14 +/- 9%) was defined by age > or = 50 yr with either ESR > or = 60 mm/h or the combination of modified functional class (1-7) > or = 4 with a disease duration > or = 7 months. An intermediate group (n = 38; 3-yrER 79 +/- 6%) was defined by (a) age > or = 50 yr and low or moderate disease activity, (b) age < 50 yr and more strenuous job-related physical requirements, (c) age < 50 yr and less strenuous work, but joint count > or = 15. No case of PWD occurred in 21 individuals aged < 50 yr with a joint count < 15 and less physically demanding jobs. PWD occurs early in a substantial number of patients with RA. RECPAM defines risk profiles that can readily be applied in actual clinical situations and allow an estimation of the risk of PWD at different time points using the resulting Kaplan-Meier curves.

Prognostic value of neural invasion in rectal carcinoma: A multivariate analysis on 339 patients with curative resection

To determine whether neural invasion or other clinico-pathological factors are prognostic, we performed a retrospective study on 339 rectal carcinomas. The overall 5-year survival was 62%. In the multivariate analysis, age over 60 years, a distance from the anal verge of less than 6 cm, the number of positive lymph nodes, neural invasion and tumour penetration were found to be prognostic. A scoring system identified five prognostic groups of patients. Neural invasion is an independent prognostic factor in our scoring system and it is suggested that this parameter should be taken into consideration for postsurgical treatment.

Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma

We report the palliative effectiveness of a hypofractionated radiotherapy regimen in patients with poor prognosis high grade glioma. Thirty-eight elderly, and/or disabled patients received radiotherapy to a dose of 30 Gy in 6 fractions over 2 weeks to a planning target volume defined by the enhancing tumour and a 2-cm margin. The median survival was 6 months with a 1-year survival rate of 23%. Treatment was without acute toxicity. One month after radiotherapy, functional status, assessed using a verbally administered Barthel index, improved in 38% and remained stable in a further 39% of surviving patients. At 3 months 39% of surviving patients had improved and a further 12% remained stable. We conclude that in the poor prognostic group of patients with high grade glioma hypofractionated partial brain radiotherapy is well tolerated, convenient and provides effective palliation in a proportion of patients. Comparison with conventional radiotherapy or symptomatic care alone require further evaluation in randomised studies.

Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma

We report the palliative effectiveness of a hypofractionated radiotherapy regimen in patients with poor prognosis high grade glioma. Thirty-eight elderly, and/or disabled patients received radiotherapy to a dose of 30 Gy in 6 fractions over 2 weeks to a planning target volume defined by the enhancing tumour and a 2-cm margin. The median survival was 6 months with a 1-year survival rate of 23%. Treatment was without acute toxicity. One month after radiotherapy, functional status, assessed using a verbally administered Barthel index, improved in 38% and remained stable in a further 39% of surviving patients. At 3 months 39% of surviving patients had improved and a further 12% remained stable. We conclude that in the poor prognostic group of patients with high grade glioma hypofractionated partial brain radiotherapy is well tolerated, convenient and provides effective palliation in a proportion of patients. Comparison with conventional radiotherapy or symptomatic care alone require further evaluation in randomised studies.