Dietary fat consumption and survival among women with breast cancer.

An historical prospective study was conducted to examine the relationship of dietary fat intake to disease progression and length of survival of 953 women with breast cancer. Estimates of monthly fat intake were based on patient responses about usual frequency of consuming 33 foods and beverages prior to symptom onset. Average estimated monthly fat intake did not vary by stage of disease at diagnosis. When controlling for disease stage and patient age at diagnosis, the estimated risk of death at any time increased 1.4-fold for each 1,000 g in monthly fat intake. Separate analysis by disease stage showed this association to be most pronounced for subjects with advanced disease. The need for future studies to incorporate clinical and pathologic factors in the analysis, to distinguish between sources of dietary fat intake, and to ascertain dietary patterns subsequent to breast cancer diagnosis was noted.

Relative reliability of five serially measured markers for prognosis of progression in prostate cancer.

During an 8-year period, 1,065 serum specimens were collected from 79 patients with prostate cancer of stages B2 to D1 (group I) and 51 patients with newly diagnosed stage D2 prostate cancer (group II) to evaluate statistically the relative reliability of elevated tumor-associated markers for progressive disease in prostate cancer. Forty of the group I patients and 21 of the group II patients presented a clinical progression of disease during follow-up. With the use of Gail's modification of Cox's regression model, serial acid phosphatase (AcP), total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), prostatic acid phosphatase (PAP), and prostate-specific antigen (PA) were analyzed. Results from group I patients revealed that only PA (P = .0002) and PAP (P = .0684) were prognostically important markers for detection of imminent disease progression. However, all markers were prognostically important in group II patients. Comparative studies indicated that PA (P = .0052) and PAP (P = .0359) were the more reliable markers for group I patients, whereas PA (P less than .0001), BAP (P = .0007), and PAP (P = .0206) were the more reliable markers for group II patients. Multivariate analyses revealed that, after adjustment for the effect of PA, no other marker was significantly related to the risk of progression. Elevated PA levels were predictive of increased risk 6 months before disease progression in group I patients only (P less than .0001). Overall, the apparent order of prognostic reliability for disease progression was found to be PA greater than PAP greater than BAP greater than AcP greater than TAP.

Prognostic factors in patients with advanced stage prostate cancer.

The relationships of 13 potential prognostic factors to objective response to treatment and survival time were investigated, using data gathered on 1,020 patients with advanced stage prostate cancer who have participated in the clinical trials of the National Prostatic Cancer Project. Multivariate statistical analyses revealed that previous hormone response status, analgesics, pain, elevated acid phosphatase, and anemia were the important, independent prognostic factors for objective response to treatment. For survival time, the significant prognostic factors were previous hormone response status, anorexia, elevated acid phosphatase, pain, elevated alkaline phosphatase, obstructive symptoms, tumor grade, performance status, anemia, and age at diagnosis. It is recommended that future treatment protocols for advanced stage prostate cancer take into account heterogeneity of the treatment groups with respect to these factors, either through the design of the protocol, or at the time of analysis.

Expression of an unusual isozyme of lactate dehydrogenase in the serum of cancer patients and comparison with carcinoembryonic antigen.

Two studies reported here demonstrate a statistically significant association between metastatic cancer and the appearance of the k isozyme of lactate dehydrogenase in serum of affected patients. The first study included 190 coded samples from three types of cancer patients and matched controls; the second included 155 preoperative and 200 postoperative colorectal cancer patients. In the second, plasma carcinoembryonic antigen was compared with serum k isozyme of lactate dehydrogenase as an indicator of the presence of metastatic cancer. This comparison showed that both markers were independently useful for assessing patient status and predicted that a combination of the two should be a better discriminator for the presence of metastases than either marker alone.

Prognostic importance of prostate-specific antigen for monitoring patients with stages B2 to D1 prostate cancer.

To evaluate the prognostic value of prostate-specific antigen (PA) for detection of tumor growth after definitive therapy, 602 sera from 70 patients with stages B2 to D1 prostate cancer (26 of whom recurred) were analyzed in a blind study. Using Cox's proportional-hazards model, a highly significant association was found between serially measured PA and disease-free survival time (p = 0.0002). A positive predictive value of 100% was found for some markedly elevated PA levels and confirmed recurrence of disease. In fact, this study suggested that once a PA level of 88 ng/ml was reached, there was an average time of less than 2 months before a recurrence was clinically confirmed. Tumor growth in patients who recurred was indicated by a PA elevation before recurrence in 92% (24 of 26) as opposed to 20% (9 of 44) in disease-free patients. Additionally, in these 24 of 26 patients, levels of PA were elevated 12 months (mean lead time) before a confirmed disease recurrence. In patients who were still disease free, serial PA appeared to increase concurrently with putative tumor growth as shown by the initial surgical stage. Generally, the greater the PA level the more advanced was the stage of disease (B2 to D1). These data suggest that PA may be a useful adjuvant marker for monitoring tumor growth in patients with regionally confined prostate cancer.

The impact of aggressive debulking surgery and cisplatin-based chemotherapy on progression-free survival in stage III and IV ovarian carcinoma.

Forty consecutive patients with stage III and IV invasive ovarian carcinoma were treated on a phase II protocol consisting of optimal debulking surgery, induction cisplatin, cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy, 6-month interval laparoscopy, reinduction cisplatin, PAC chemotherapy, and second-look procedure. All 40 patients have either disease progression or have completed the 12-month protocol. Eighty-seven percent of the patients (35) underwent optimal (less than or equal to 2 cm residual) debulking surgery before chemotherapy, in spite of the fact that 50% (20) were referred to Roswell Park Memorial Institute (RPMI) as inoperable after initial surgery elsewhere. There were no postoperative deaths and chemotherapy was started in less than or equal to 14 days in 97% of the patients. Of the 40 patients, 30% (12) achieved a pathologic complete remission (11) or a clinical complete remission (one patient refused second-look surgery). The estimated 3-year survival rate was 62%, but the 3-year progression-free survival rate was only 29%. The median survival time was 48 months. The estimated 3-year progression-free survival rate was 31% for residual disease less than or equal to 2 cm. For the five patients with residual disease greater than 2 cm, four died within 3 years. The median survival time of patients with less than or equal to 2 cm residual disease was 48 months, as compared with 21 months for those with greater than 2 cm residual disease. Although the estimated 3-year survival rate of 62% is noteworthy, the 3-year progression-free survival rate of only 29% is probably indicative that in spite of extensive debulking surgery and cisplatin-based chemotherapy as used in this protocol, the long range proportion of patients "cured" will remain small.

A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma.

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.

Surgically documented response to intraperitoneal cisplatin, cytarabine, and bleomycin after intravenous cisplatin-based chemotherapy in advanced ovarian adenocarcinoma.

Thirty-one evaluable patients with stages III and IV invasive ovarian adenocarcinoma were treated on a phase II protocol of second-line intraperitoneal cisplatin, cytarabine, and bleomycin. All 31 patients received first-line intravenous (IV) cisplatin-based chemotherapy; the size of the residual cancer was documented surgically before intraperitoneal chemotherapy in all patients. Response to intraperitoneal chemotherapy was documented by a third-look laparotomy in all patients not evidencing progression of disease clinically. There were eight responses (26%): five surgical complete responses and three surgical partial responses. Responders were patients with stage III ovarian cancer, small residual disease of less than or equal to 1 cm (primarily less than or equal to 5 mm), and patients who previously had responded to cisplatin-based IV chemotherapy. Of the 15 patients with stage III ovarian cancer, residual disease less than or equal to 1 cm, and those who had responded to first-line IV cisplatin-based chemotherapy, 53% (eight) responded to second-line intraperitoneal chemotherapy. Intraperitoneal chemotherapy as used in this phase II protocol would appear to be an effective second-line treatment in advanced ovarian cancer in this specific subset of patients.

A phase II trial of 5-fluorouracil and high-dose intravenous leucovorin in gastric carcinoma.

Twenty-eight patients with advanced measurable gastric carcinoma were treated with leucovorin (dl-CF; folinic acid; dl-5-formyltetrahydrofolic acid) 500 mg/m2 administered as a two-hour infusion and 5-fluorouracil (5-FU) 600 mg/m2 intravenous (IV) push midinfusion. Treatment was administered weekly for 6 weeks followed by a 2-week rest. Twenty-five patients were evaluable for response. Twelve of them had received previous combination chemotherapy that included 5-FU. Median age was 59 years, and median Eastern Cooperative Oncology Group (ECOG) performance status was 2. Three patients had partial responses and two of them had been treated previously with 5-FU. Twelve patients had stable disease. Five of these patients had subjective improvement with improved performance status and/or decreased dysphagia. The 95% confidence interval for response is 3% to 32%. Median survival time for all 28 patients enrolled in the study was 22 weeks. Toxicity was moderate and consisted primarily of diarrhea. Myelosuppression, skin rash, and increased lacrimation also occurred. Plasma concentrations of the active reduced folates, I-CF and 5-methyltetrahydrofolic acid (5-CH3FH4), were greater than the 10 mumol/L levels that potentiate 5-FU activity in in vitro models, for more than four hours in all five patients in whom pharmacokinetics were studied. 5-FU and high-dose dl-CF has activity in patients with gastric carcinoma including patients who had previously progressed on 5-FU-containing combinations. Further study in a larger patient population is necessary to determine the usefulness of this regimen in gastric carcinoma.

Prognostic significance of karyotypic abnormalities in B cell chronic lymphocytic leukemia: an update.

Cytogenetic analyses by G-banding and/or Q-banding techniques of leukemic B cells were performed in 102 patients with chronic lymphocytic leukemia (CLL), including six with prolymphocytic leukemia (PLL), one with hairy cell leukemia (HCL), and one with Waldenstrom's macroglobulinemia (WM) from 1979 through 1983. Follow-up after cytogenetic study ranged from 24 to 70 months. Seventeen patients had stage 0, 10 had stage I, 31 had stage II, and 44 had stage III or IV. Adequate metaphases were obtained for karyotypic analysis in 86 (84%) of 102 patients. Of these 86 patients with adequate metaphases, 43 had normal karyotypes (50%) and 43 had abnormal karyotypes (50%), of which trisomy 12 was the most frequent. Ten patients had trisomy 12 as the sole abnormality, 14 had trisomy 12 in combination with other abnormalities, and the remaining 19 had other abnormalities without trisomy 12. Abnormal karyotypes were more frequently associated with patients with advanced stages than those with early stages of the disease. Response rate to chemotherapy was significantly higher in patients with normal karyotypes than in those with abnormal karyotypes. Of eight patients who subsequently developed Richter's syndrome, seven initially had complex karyotypic changes with or without trisomy 12. These observations suggest that the chances of development of Richter's syndrome in CLL patients with multiple chromosome changes may be much higher than in those with either simple trisomy 12 or a normal karyotype. Mean frequency of abnormal metaphases was significantly higher in patients with complex trisomy 12 in combination with other changes than in those with trisomy 12 as the sole abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy.

Methicillin-resistant coagulase-negative staphylococci have become increasingly responsible for febrile episodes in cancer patients, often necessitating the addition of vancomycin to an aminoglycoside-containing broad-spectrum antibiotic regimen. A total of 229 courses of antibiotic therapy in 229 patients were evaluated for nephrotoxicity associated with the administration of an aminoglycoside and/or vancomycin. The incidence of nephrotoxicity observed in patients administered an aminoglycoside (Group A) was 18 percent; vancomycin (Group B) 15 percent; and an aminoglycoside concurrently with vancomycin (Group C) 15 percent. The following pharmacokinetic/dosing factors were significantly associated with increased nephrotoxicity in the groups: baseline serum creatinine level, mean daily dose during the first three days of therapy (Group B), and elevated serum trough aminoglycoside or vancomycin concentrations (2 micrograms/ml or more or 10 micrograms/ml or more, respectively). No cumulative nephrotoxicity was demonstrated with the concurrent administration of vancomycin and an aminoglycoside. A higher incidence of nephrotoxicity was seen in Group C (42 percent) and Group B (27 percent) patients, in whom trough serum vancomycin concentrations were 10 micrograms/ml or more.

The clinical significance of pathological findings in surgically resected margins of the primary tumor in head and neck carcinoma.

Two hundred seventy (270) consecutive surgical patients treated at Roswell Park Memorial Institute for carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx between 1977 and 1982 were reviewed to determine the relationship between pathological findings at the surgical margins of the primary tumor and the incidence of local recurrence and clinical outcome. The estimated 5-year disease-free survival rate was 39% for patients with free surgical margins (10%--hypopharynx, 30%--oropharynx, 40%--oral cavity, and 53%--larynx) and 7% for not-free surgical margins. Patients with free surgical margins and with well-differentiated squamous cell carcinoma had better prognosis than those patients with moderately- and poorly-differentiated carcinomas. The local recurrence rate for Stage T1 and T2 lesions with free surgical margins was 17%, compared with 27% for Stages T3 and T4. The results of this study indicate that pathological evidence of complete excision of the primary tumor is important and attempts should be made to obtain pathological clearance. The local recurrence rate for Stage T3 and T4 lesions is high. Adjuvant therapy is indicated and post-operative radiotherapy is recommended.

The effect of local recurrence on survival time in adult high-grade soft tissue sarcomas.

Data gathered on 262 adults with high-grade soft tissue sarcoma, operated on at the same institution for curative intent, were used to study formally, and to quantitate for the first time, the relationship between local recurrence of the tumor and survival time. Using Cox's proportional hazards model with a time-dependent covariate representing the local recurrence of the tumor, it was found that local recurrence is significantly associated with a shorter survival time (estimated relative risk (relative hazard) = 2.5, p less than 0.0001). The estimated 5 yr survival rate and median survival time for patients without a local recurrence were 44% and 42 months, respectively, while the corresponding figures for patients with a local recurrence were only 26% and 28 months. Hence, a local recurrence resulted in a relative decline in the estimated 5 yr survival rate of 41%. This strong relationship continued to hold even after adjusting for several other important, time-independent prognostic variables (stage, type of surgery, type of resection, signs of sarcomatous skin invasion, and presence of postoperative fever) in a multivariable analysis. Local control of high-grade soft tissue sarcomas is vitally important for successful management of these patients.

Survival after groin dissection for malignant melanoma.

Groin dissection was performed in 158 patients with malignant melanoma (superficial dissection, 76 patients; radical dissection, 82 patients). Of 63 patients with palpable nodes, 57 patients (90%) had histologic involvement. Of 93 patients with nonpalpable nodes, 31 patients (33%) had histologically positive nodes. The 5-year survival rate for patients with histologically negative nodes (n = 69) was 77%; the 5-year survival rate for patients with histologically positive nodes (n = 89) was 43%. The respective 5-year disease-free survival rates were 72% and 34%. Of 57 patients with palpable, positive inguinal nodes, 21 patients (37%) had involvement of the deep nodes. Of 31 patients with nonpalpable, histologic involvement of the inguinal nodes, six patients (19%) had or developed involvement of the deep nodes. One of two patients with uncertain clinical status of the nodes preoperatively had positive deep nodes. In prophylactic node dissection, frozen section of the inguinal group of the nodes does not provide a reliable method, because of sampling errors, in determining microscopic involvement of the nodes and in deciding whether a superficial or radical groin dissection is to be done. For patients with positive nodes the 5-year survival rate was 48% when only the inguinal group was involved and was 28% when both inguinal and deep nodes were involved; the respective 5-year disease-free survival rates were 39% and 20%. Survival after therapeutic groin dissection may partly depend on the thoroughness of the procedure. Patients who have positive, deep nodes and who are undergoing an incontinuity dissection of the inguinal, iliac, and obturator nodes have an appreciable 5-year survival rate.

Axillary node dissection in malignant melanoma: results and complications.

Axillary node dissection was performed in 133 patients with malignant melanoma. The nodes were histologically negative for disease in 67 patients and positive in 66 patients. Disease-free survival rate varied according to the histologic and clinical status of the nodes and to the number of the nodes involved by tumor. The lymphocele rate was 7%; the wound infection rate was 5%; and the skin edge necrosis rate was 0.8%. One patient (0.8%) experienced both lymphocele and wound infection. Neurapraxia developed in the distribution of the musculocutaneous nerve in two patients (2%); this resolved completely in 3 to 4 weeks and was not observed again, since hyperextension of the arm has been carefully avoided during the procedure. Transient arm edema was noted postoperatively in five patients (4%), and the edema responded promptly and completely to elevation of the arm for 1 to 2 weeks. There was no permanent edema even after ligation and resection of the distal portion of the axillary vein (six patients). Permanent arm edema has not developed in any of the 133 patients, indicating that axillary node dissection as performed for malignant melanoma is not associated with the long-term complications occurring after mastectomy and axillary node dissection.

Melphalan, 5-fluorouracil, and medroxyprogesterone acetate in metastatic endometrial carcinoma.

Fifty consecutive patients with recurrent and metastatic endometrial carcinoma were treated with melphalan, 5-fluorouracil, and medroxyprogesterone acetate with or without tamoxifen as first-line chemotherapy. The objective response rate was 48%, with 20% complete responses. The estimated median progression-free survival time was only five months (0.5 to 65 months) with estimated two- and five-year progression-free survival rates of 16 and 13%, respectively. The estimated median progression-free survival time was 24 months for complete responders; the progression-free survival times were significantly longer than the survival times (median = four months) for all other patients (P = .0002). Whether or not the addition of cytotoxic chemotherapy to progesterone hormonal therapy for metastatic endometrial carcinoma lengthens survival time is still open to question.

Soft-tissue sarcomas of the proximal lower extremity.

Of 54 patients with soft-tissue sarcomas of the proximal part of the lower extremity, 2 patients (4%) were treated with amputation, while 52 patients (96%) were treated with limb-preserving resection. Adjuvant postoperative irradiation was applied selectively when the minimum margin was less than 2 cm (22 patients). Technical improvements in exposure, resection of involved vessels or nerve, and preservation of function permitted a high rate of limb salvage with satisfactory function. At a median follow-up of 30 months for those subjects still alive, the 5-year disease-free survival rate was 65%, and only 3 patients (6%) had had a local recurrence.

Limb salvage in soft tissue sarcomas with selective combination of modalities.

One hundred and seventy-one consecutive patients with soft tissue sarcomas were treated in the period 1977-1986. Of 144 patients with extremity sarcomas, only eight (6%) were managed with amputation. The overall estimated 5-year survival rate is 64%, and that for patients with extremity tumors is 71%. The 5-year local recurrence rate in extremity sarcomas was 6% for patients with minimum surgical margins 2 cm or greater and no further local therapy, and 6% for those with narrower surgical margins and adjuvant postoperative radiation; 80 patients (56%) were in the former group and 64 (44%) in the latter. With a selective combination of modalities, limb salvage can now be practiced in 94% of the patients with acceptable local control and survival rates.

Clinical factors and treatment parameters affecting prognosis in adult high-grade soft tissue sarcomas: a retrospective review of 267 cases.

Data on 267 adults with high-grade soft tissue sarcomas were reviewed. Male sex, large tumor size, Stage IIIC, IV A and sarcomatous skin invasion, as well as marginal excision, amputation, postoperative fever and wound infection, were found to be associated with shorter survival time. Head and neck location, multifocal growth of sarcoma. Stage IIIC, malignant skin infiltration, locally recurrent tumor as well as marginal excision and limb-sparing resection, were found to influence local control unfavorably in single factor analyses. Each of the significant variables were entered into a multivariate proportional hazards model in a stepwise manner. Stage, postoperative fever, the surgical margin and type of surgery, and sarcomatous skin changes significantly affected survival time. Local recurrence was significantly affected by the surgical margin and type of surgery, the status of tumor (primary or recurrent), stage and malignant skin infiltration.

Groin dissection in malignant melanoma.

One hundred seventeen patients with malignant melanoma who had groin dissection were reviewed. The estimated 5 year survival rate for patients with node involvement was 40 percent. For patients with involved inguinal nodes only, the 5 year survival rate was 47 percent. The estimated 5 year survival rate for patients with clinically enlarged and histologically involved nodes was 37 percent and the incidence of involved deep nodes in this group was 44 percent. For patients with clinical and histologic involvement of the inguinal and deep nodes, the estimated 5 year survival rate was 30 percent. In patients with clinical involvement of the inguinal nodes, radical groin dissection with in-continuity removal of the deep nodes appeared to improve the previously reported survival rates.