The impact of facility volume/size on breast cancer treatment and outcome

Recent studies have suggested that outcomes and survival from breast cancer are improved when definitive treatment is rendered at high-volume and/or teaching centers. Consolidation of such cases in tertiary centers, however, is often impractical and impossible. Patients often desire primary treatment of their breast cancer in their own communities. The current study was undertaken to examine the impact of treatment facility type on the treatment performed as well as on overall survival. Breast cancer treatment and survival data were available from the American College of Surgeons National Cancer Data Base. Only patients in whom no previous treatment had been rendered were included in the analysis. Data were stratified with regard to type and size of treatment facility/hospital; stage distribution; initial treatment performed; and 1-, 2-, and 5-year survival. A total of 665,409 patients were included in the current analysis. There were no significant differences in stage distribution between facility types nor was there a significant difference in the treatment performed (although there was a slight trend toward breast conservation at the larger centers). This was true overall and for each stage of cohort. There were also no significant differences in 1-, 2-, and 5-year survival rates overall and at any stage (although again, there was a slight trend toward a minimal survival advantage at the larger centers). There was no significant impact of facility size or type on either breast cancer treatment performed or overall survival. There was no evidence that more "advanced" treatments were offered at larger centers nor was there evidence of improved outcome/survival at larger centers. Care can be rendered safely, efficiently, and effectively in the community setting.     

Randomized, dose-finding phase III study of lithium gamolenate in patients with advanced pancreatic adenocarcinoma

BACKGROUND: Chemotherapy for pancreatic cancer offers small survival benefits and considerable side-effects. Unsaturated fatty acids have an antitumour effect in experimental studies; in phase II studies few side-effects were seen. METHODS: In this group-sequential, open-label, randomized study, 278 patients with a diagnosis of inoperable pancreatic cancer were treated with either oral (700 mg daily for 15 days), low-dose (0.28 g/kg) or high-dose (0.84 g/kg) intravenous lithium gamolenate (LiGLA). The primary endpoint was survival time from randomization using Kaplan-Meier estimates. RESULTS: Median survival after oral and low-dose intravenous treatment was 129 and 121 days respectively. Median survival after high-dose intravenous treatment was 94 days. A good Karnofsky score and the absence of metastases were associated with increased survival. Haemolysis, a marker of rapid infusion, was associated with a median survival time of 249 days in the low-dose intravenous group. CONCLUSION: Oral or low-dose intravenous LiGLA led to survival times similar to those of other treatments for pancreatic cancer although one subgroup (low-dose intravenous LiGLA with haemolysis) had longer survival. High-dose intravenous treatment appeared to have an adverse effect. Systemic treatment with LiGLA cannot be recommended for the treatment of pancreatic cancer.     

Combined intra-arterial and systemic chemotherapy for recurrent malignant brain tumors.

Seventy-nine patients harboring recurrent brain tumors received four cycles of infraophthalmic carotid injections of 160 mg of carmustine. Two milligrams of intravenous vincristine and 50 mg of oral procarbazine was also administered three times daily for 1 week in conjunction with each BCNU treatment. The response rate was 60% with a median survival for patients with astrocytomas, anaplastic astrocytomas, and glioblastomas of 32, 20, and 6.5 months, respectively. The median survival of the responding patients was 20 months, and the survival at 30 months was 45%. The survival in patients not responding to treatment was 5 months, reflecting the natural history of the tumor. There have been no deaths related to the treatment procedure. No incidents of severe or permanent eye complications or leukoencephalopathy were observed. Based on multivariate survival analysis, only patients with a good performance status who are not steroid dependent are candidates for this treatment.     

Factors determining prolongation of rat heart allograft survival by perioperative injection of donor spleen cells

Previously, we have shown that a perioperative injection of donor mononuclear cells in combination with cyclosporine treatment on day 2 after transplantation prolongs heart allograft survival in rats. In this study we determined whether the efficacy of this treatment was influenced by the same factors that have been shown to affect the efficacy of preoperative administration of donor cells. The effect of the following factors were investigated: dosage and repetition of the donor cell injection, viability of the donor cells, immunosuppressive drugs other than cyclosporine, and the rat strain combination. We found that there was an optimal dosage of donor cells; dosages of 4 x 10(7) or 1 x 10(8) cells gave the best heart graft survival. Repetition of the donor cell injection was not useful. Reducing viability of the cells by irradiation did not abrogate the prolonged graft survival, whereas killing of the cells did. Methylprednisolone, azathioprine, or cyclophosphamide in combination with the perioperative donor cell injection did not prolong heart graft survival in comparison with treatment with the drug only. The efficacy of this treatment was also influenced by the rat strain combination. In some combinations, this treatment prolonged graft survival, whereas in others an effect was absent or undetectable. Importantly, this treatment never adversely affected graft survival. We conclude that the efficacy of this treatment is influenced by similar factors as found for preoperative treatment with donor cells. A major advantage of this treatment over preoperative blood transfusions is that it avoids sensitization.     

Treatment of locally advanced prostate cancer--the case for radical prostatectomy

The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called 'watchful waiting'. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series--based on good clinical case selection--approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatment.     

Re-evaluation with abridged life tables of the prognosis of lung cancer patients who underwent surgical therapy]

Some lung cancer patients after surgical treatment die as a result of pneumonia or cardiac failure without recurrence of lung cancer months or years after surgery because many such patients are aged or have decreased lung function. Surgical treatment may be partly to blame for these deaths. In this article, to evaluate the contribution of surgical treatment to deaths resulting from other disease, we calculate predicted survival rates using abridged life tables and compute relative survival rates. From 1952 to 1985, a total of 1289 lung cancer patients underwent surgical resection of lung cancer in our department. We calculated some kind of survival rates according to age, stage, and operative procedure. Each case was classified according to age (5-year periods), year of operation (5-year periods), and sex. The 5-year survival rate indicated by the abridged life tables in each class was regarded as the 5-year predicted survival rate of the case. The mean of 5-year predicted survival rates of all cases in a group was regarded as being the 5-year predicted survival rate of the group. The ratio (actual survival rate of the group/predicted survival rate of the group) was also calculated. The ratio of the patients who had stage O, I, or II diseases tended to decrease according to age. This fact supposed that the number of deaths resulting from other diseases with no recurrence of lung cancer in which surgical treatment contributed to death increased in the elderly. In the other hand, this tendency did not exist in the patients who had stage IIIA diseases.     

Treatment options for patients with stage D1 (T0-3,N1-2,M0) adenocarcinoma of prostate

Three hundred six patients with adenocarcinoma of the prostate underwent pelvic lymphadenectomy and had Stage D1 (T0-3,N1-2,M0) disease; 171 patients underwent radical retropubic prostatectomy with or without immediate adjuvant therapy (hormonal or radiation or both) or conservative (hormonal or radiation or both) treatment alone (n = 135). Follow-up was one-half to eighteen and one-half years (mean, 5 yrs). Immediate adjuvant orchiectomy significantly (P = 0.01) improved survival (87.4% at 10 years) and nonprogression rates for patients who underwent radical prostatectomy, but not for those who had lymphadenectomy. Overall patient survival was significantly better (P = 0.005) after prostatectomy than lymphadenectomy. Residual disease (n = 43) in patients who underwent prostatectomy and received adjuvant treatment (orchiectomy or radiation or both) did not affect disease outcome. Bilateral pelvic lymphadenectomy and radical prostatectomy with immediate adjuvant orchiectomy provided survival comparable to the expected survival; conservative treatment alone was associated with rapid disease progression and poor survival and significantly (P = 0.02) higher local morbidity.     

Multimodal therapy for squamous carcinoma of the oesophagus.

BACKGROUND: The results of surgical treatment for oesophageal squamous cell cancer have improved over recent decades, but the long-term prognosis for patients with tumours of stage II or higher is still unsatisfactory. While uncontrolled series of adjuvant or neoadjuvant treatment have reported favourable survival rates, the true benefit of multimodal treatment can be determined only by randomized controlled trials. METHODS: The literature was searched for prospective randomized controlled trials (PRCTs) examining the effect of neoadjuvant or adjuvant treatment on the long-term survival of patients with squamous cell cancer of the oesophagus. RESULTS: More than 30 PRCTs studying multimodal treatment concepts aimed at improving the prognosis of squamous cell carcinoma of the oesophagus were identified. These trials have not documented improved survival by adjuvant radiotherapy or chemotherapy. Following neoadjuvant radiotherapy or chemotherapy (or a combination of both), resectability of squamous cell carcinoma is not increased, the postoperative mortality rate appears to be higher and survival is not prolonged. CONCLUSION: Past multimodality protocols have not improved the prognosis of squamous carcinoma of the oesophagus. Careful design and reporting, together with strict control of surgical procedures, should allow more meaningful analysis of future multimodal treatment studies. At present, neoadjuvant or adjuvant treatment cannot be recommended outside such clinical protocols.     

Renal replacement therapy in type 2 diabetic patients: 10 years' experience.

The objective of this study was to determine the impact of renal transplantation and hemodialysis treatment on outcome of elderly diabetic patients with end-stage renal disease (ESRD) among other factors related to survival. Results of treatment of ESRD in 78 patients with non-insulin-dependent diabetes mellitus (type 2) showed a survival rate of 58% at 1 year and 14% at 5 years, independent of treatment modality. Patients who received a renal allograft had a higher survival rate as compared with patients on hemodialysis treatment (5-year survival, 59% v 2%; P < 0.005). Diabetic patients with a history of myocardial infarction, stroke, or peripheral gangrene before onset of renal replacement therapy had a worse prognosis in comparison to patients without vascular complications (5-year survival, 2% v 21%; P < 0.05). Analysis of patients who survived less than 6 months and more than 24 months was performed. Long-term survivors were slightly younger, had diabetes for a shorter period, and showed a better metabolic control of diabetes mellitus. Sixteen long-term survivors received a renal allograft. In contrast, only three short-term survivors were transplanted. Furthermore, short-term survivors also had a greater than 70% incidence of severe vascular complications before renal replacement therapy. A history of myocardial infarction, stroke, or peripheral gangrene is an independent predictor of decreased survival, irrespective of whether the patients were transplanted or maintained on chronic hemodialysis treatment. In contrast, renal transplantation improved survival of elderly diabetic patients without vascular complications and should be the treatment of choice in this specific group of patients.     

Survival after stereotactic biopsy of malignant gliomas

For many patients with malignant gliomas in inaccessible or functionally important locations, stereotactic biopsy followed by radiation therapy (RT) may be a more appropriate initial treatment than craniotomy and tumor resection. We studied the long term survival in 91 consecutive patients with malignant gliomas diagnosed by stereotactic biopsy: 64 had glioblastoma multiforme (GBM) and 27 had anaplastic astrocytoma (AA). Sixty-four per cent of the GBMs and 33% of the AAs involved deep or midline cerebral structures. The treatment prescribed after biopsy, the tumor location, the histological findings, and the patient's age at presentation (for AAs) were statistically important factors determining patient survival. If adequate RT (tumor dose of 5000 to 6000 cGy) was not prescribed, the median survival was less than or equal to 11 weeks regardless of tumor histology or location. The median survival for patients with deep or midline tumors who completed RT was similar in AA (19.4 weeks) and GBM (27 weeks) cases. Histology was an important predictor of survival only for patients with adequately treated lobar tumors. The median survival in lobar GBM patients who completed RT was 46.9 weeks, and that in lobar AA patients who completed RT was 129 weeks. Cytoreductive surgery had no statistically significant effect on survival. Among the clinical factors examined, age of less than 40 years at presentation was associated with prolonged survival only in AA patients. Constellations of clinical features, tumor location, histological diagnosis, and treatment prescribed were related to survival time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased skin flap survival and arterial dilation by calcitonin gene-related peptide. A study in the pig

Calcitonin gene-related peptide (CGRP), a recently discovered neuropeptide, is a potent vasodilator and increases blood flow in many vascular beds. The effect of CGRP treatment was investigated in critical pig pedicle and island flaps. Prior to pharmacological treatment the peroperative circulation border was estimated with fluorescein. Intradermal or intraarterial flap treatment with CGRP was given. Control flaps were untreated or injected with saline. Increased or decreased survival was calculated as the difference between the peroperative fluorescein penetration border and the survival border one week after surgery. CGRP treatment significantly increased the survival of both random pedicle and island flaps. CGRP doses as low as 3 ml x 10(-14) M (equal to 0.03 fmoles) increased the survival of random pedicle flaps. In 4 untreated pigs the deep circumflex iliac arteries were excised and artery ring preparations were studied in vitro. A dose-dependent relaxation of artery rings was noted between 10(-9) M and 10(-7) M CGRP.     

Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer

SUMMARY BACKGROUND DATA: To analyze the effects of a treatment program of intraoperative electron beam radiation therapy (IOERT) and external beam radiation therapy and chemotherapy on the outcome of patients with unresectable or locally advanced pancreatic cancer. METHODS: From 1978 to 2001, 150 patients with unresectable and nonmetastatic pancreatic cancer received IOERT combined with external beam radiation therapy and 5-fluorouracil-based chemotherapy for definitive treatment. RESULTS: The 1-, 2-, and 3-year actuarial survival rates of all 150 patients were 54%, 15%, and 7%, respectively. Median and mean survival rates were 13 and 17 months, respectively. Long-term survival has been observed in 8 patients. Five patients have survived beyond 5 years and 3 more between 3 and 4 years. There was a statistically significant correlation of survival to the diameter of treatment applicator (a surrogate for tumor size) used during IOERT. For 26 patients treated with a small-diameter applicator (5 cm or 6 cm), the 2- and 3-year actuarial survival rates were 27% and 17%, respectively. In contrast, none of the 11 patients treated with a 9-cm-diameter applicator survived beyond 18 months. Intermediate survival rates were seen for patients treated with a 7- or 8-cm-diameter applicator. Operative mortality was 0.6%, and postoperative and late complications were 20% and 15%, respectively. CONCLUSIONS: A treatment strategy employing IOERT has resulted in long-term survival in 8 of 150 patients with unresectable pancreatic cancer. Survival benefit was limited to patients with small tumors. Enrollment of selected patients with small tumors into innovative protocols employing this treatment approach is appropriate.     

Long-Term Survival After Complete Resection and Repeat Resection in Patients With Adrenocortical Carcinoma

Background: One of the key issues in the treatment of adrenocortical carcinoma is the efficacy of repeat resection of local recurrence and metastatic disease in affected patients. Options in the treatment of locally recurrent or metastatic disease are limited because chemotherapy and radiotherapy generally do not provide any significant prolongation in survival in treated patients.Methods: A series of 113 patients who presented to Memorial Sloan-Kettering Cancer Center for treatment of adrenocortical carcinoma are presented.Results: The median overall survival for all 113 patients was 38 months (5-year survival, 37%). Patients presenting with early stage I or II disease (n = 57) had a median survival of 101 months (5-year survival, 60%), whereas those with late stage III or IV disease (n = 56) had a median survival of 15 months (5-year survival, 10%). Patients who had complete primary resection (n = 68) had a median survival of 74 months (5-year survival, 55%), whereas those with incomplete primary resection (n = 45) had a median survival of 12 months (5-year survival, 5%). Resection of locally recurrent or distant metastatic disease was performed in 47 of these patients. Patients who had a complete second resection had a median survival of 74 months (5-year survival, 57%), whereas those with incomplete second resection had a median survival of 16 months (5-year survival, 0%).Conclusions: Improved survival is seen in patients who present with early stage and have complete primary resection. Patients who undergo complete repeat resection of local recurrence or distant metastasis also have improved survival. Complete repeat resection was more readily accomplished in discrete distant metastatic lesions compared with bulky local recurrences.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999     

Palliative radiation schedules with and without chemotherapy in advanced carcinoma of the esophagus

In a prospective randomized study, 272 patients with advanced oesophageal cancer were treated with radiation and bleomycin or vinblastine or a combination of both cytostatics. Two radiation schedules were tested, the one involving larger fractions in a shorter period of time. Evaluation of the treatment results showed that 67% of patients experienced significant relief of dysphagia. The median survival was 3 months and the 1-year survival 7%. No statistical difference in survival was noted among the different chemotherapy or radiation groups (level of significance 5%). It was concluded that monochemotherapy as given in this study made no difference in the treatment result. The larger radiation fraction and shorter treatment time schedule was as effective as the more conventional schedule and is the preferred treatment because of the shorter hospitalization period. A pharyngostomy tube proved effective in feeding the patients. Oesophageal cancer is a systemic disease and polychemotherapy will have to play a prominent part in a multimodality treatment approach if results are to improve.     

Short-term suppression of the xeno-immune response with mCTLA4-Fc treatment

Abstract: A murine CTLA4-Fc chimeric fusion protein was used to determine if inhibition of the CD28-B7 pathway for T-cell activation could result in prolonged or indefinite survival of pancreatic islet xenografts in mice. B6AF1 recipients of Wistar rat pancreatic islet xenografts that received short-term mCTLA4-Fc treatment had prolonged graft survival (28 days vs. 9 days) but all animals rejected their grafts. This survival advantage was similar to that achieved with short-term depletion of CD3+ or CD4+ T cells with 145.2C11 (median graft survival 21 days) or GK1.5 mAb (median graft survival 33 days), respectively. Combined GK1.5, 145.2C11, and mCTLA4-Fc treatment for the first 2 weeks post-transplant and maintenance therapy with GK1.5 and mCTLA4-Fc for the next 4 weeks produced the best results (median survival 63 days). However, islet xenografts were rapidly rejected upon cessation of treatment. Unlike in allografts, short-term inhibition of the CD28-B7 pathway with mCTLA4-Fc did not result in long-term rat xenograft survival. This suggests that the conditions necessary for quenching xenograft rejection and inducing tolerance differ significantly from those found in allotransplantation and acquired xenograft tolerance may be difficult to achieve.     

Non-Hodgkin's lymphoma of the head and neck: a 30-year experience at the University of Florida

BACKGROUND: Outcome in previously untreated patients with non-Hodgkin's lymphoma of the head and neck needed to be assessed. METHODS: A retrospective review was performed of 79 patients with stage I or II non-Hodgkin's lymphoma of the head and neck treated between 1964 and 1994 with radiotherapy (RT) or combined modality therapy (CMT) at the University of Florida. Freedom from relapse, cause-specific survival, and absolute survival were analyzed by the Kaplan-Meier method. Patterns of failure were defined, and the relationship between dose and infield recurrence was studied. Histology was classified as low grade or intermediate/high grade. RESULTS: At 10 years, absolute survival for patients with low-grade lymphoma treated with RT was 45%; absolute survival for patients with intermediate/high-grade lymphoma was 41% for those treated with RT and 57% for those who received CMT. Twenty-seven patients had a recurrence of lymphoma after initial treatment. Twenty patients (74%) had recurrences outside the radiation treatment field; 90% of these failures were in predictable sites that would be included in comprehensive lymphatic irradiation fields (Waldeyer's ring, mantle, and whole abdomen). No clear dose response was observed. Multivariate analysis showed that patients with tumors <5 cm in diameter had improved cause-specific survival, absolute survival, and freedom from relapse compared with patients with tumors > or = 5 cm in diameter. CONCLUSIONS: Patients with non-Hodgkin's lymphoma in the head and neck with tumors > or = 5 cm in diameter appear to have a worse prognosis than those with smaller tumors. The patterns of failure suggest that initial treatment with comprehensive lymphatic irradiation fields could potentially eliminate the majority of treatment failures.     

Ewing's sarcoma. Prognostic factors, disease control, and the reemerging role of surgical treatment

Advances in the treatment of Ewing's sarcoma have been dramatic. Present treatment protocols control local disease by radiotherapy, surgery, or both; systemic spread is limited by aggressive multiagent chemotherapy. In patients with localized osseous Ewing's sarcoma, five-year survival rates now range from 54% to an estimated 74%. With late relapse not uncommon, control of the primary lesion is critical to long-term survival. Several studies now show improved local control and possibly improved survival of patients with surgical treatment of primary osseous Ewing's sarcoma.     

Therapie des lokal fortgeschrittenen Prostatakarzinoms

The management of clinically locally advanced prostate carcinoma (cT3) remains a controversial issue. The clinical stage cT3 consists of a mixture of overstaged T2 carcinomas but also contains lymph node-positive cases. Treatment options consist of radical prostatectomy, external beam radiotherapy, hormonal deprivation (early or delayed) and the so-called watchful waiting. In many cases multimodal therapy is used. Radical prostatectomy in the clinical stage T3 can achieve acceptable tumour-specific survival rates if patients are well selected. In this way, tumour-specific survival rates can be reached for pT3 patients which closely approach those of pT2 cases. In lymph node-positive cases after radical prostatectomy adjuvant hormonal treatment can prolong survival, but not in lymph node-negative cases. A benefit of adjuvant radiotherapy after radical prostatectomy has not been proven. Although it can postpone or prevent biochemical recurrence, it does not prolong overall survival. Treatment of stage cT3 by external beam radiotherapy alone results in unfavourable tumour-specific survival rates. In these cases definite improvement can be achieved by adjuvant androgen deprivation with LHRH analogues. If in case of severe comorbidity or advanced age primary hormonal treatment is chosen, early vs deferred treatment seems to prolong survival marginally.     

Pulmonary metastasectomy for uterine cervical cancer: a multivariate analysis

BACKGROUND: This study evaluated the results of resection of pulmonary metastases from cervical cancer. METHODS: A total of 7,748 patients with primary stage Ib or II cervical cancer underwent curative initial treatment consisting of radical hysterectomy or radiotherapy in 22 hospitals. Of the 7,748 patients, 29 (0.37%) patients had pulmonary metastases, which were detected after a disease-free period after initial treatment (radical hysterectomy or radiotherapy) and were resected with the intention to cure by June 30, 1998. RESULTS: The 5-year disease-free survival rate after pulmonary metastasectomy for all patients was 32.9%. Patients with one or two pulmonary metastases had a 5-year disease-free survival rate of 42.2% compared with 0% for patients with three or four metastases (p = 0.0003). Patients with squamous cell cancers had a 5-year disease-free survival rate of 47.4% compared with 0% for patients with adenosquamous cell cancers or adenocarcinoma (p = 0.0141). On multivariate analysis, the significant prognostic variables for disease-free survival were two or fewer metastases (p = 0.0232) and squamous cell cancer (p = 0.0168). CONCLUSIONS: Cervical cancer patients with pulmonary metastases after initial treatment (radical hysterectomy or radiotherapy) could expect to achieve long-term disease-free survival by pulmonary metastasectomy when there are two or fewer metastases diagnosed as squamous cell cancer.     

Thyroid anaplastic tumor: our experience

We report our experience over the past 10 years in the treatment of thyroid anaplastic carcinoma analysing retrospectively 21 cases of surgical treatment (7 total thyroidectomies, 12 partial resection of the tumours and 2 biopsies). We consider the prognosis, which is invariably fatal, with no survival at 19 months and a mean survival of only 9 months, and assess the validity of a combined therapeutic approach (surgery + radiotherapy + chemotherapy) to increase survival and, above all, the patient's quality of life. The importance is stressed of through monitoring of risk factors consisting in concomitant or previous benign or malignant thyroid disease, considering total thyroidectomy to be necessary in principle for any variety of thyroid cancer. Lastly, we examine the survival trend in terms of residual disease and the presence or otherwise of remote metastases.