Initial Curative Treatment Research Articles

Survivorship patterns of a large nationwide cohort of elderly veterans with colorectal cancer

13525 Background: Administrative databases are not designed to permit cancer researchers to readily follow patients from the period pre-diagnosis through initial curative intent treatment, adjuvant therapy, post-treatment follow-up, to either death or loss to follow-up. One major hurdle to cancer research using such databases has been the lack of data such as stage at diagnosis, and histopathologic type and grade. A second major hurdle is that many patients use more than one system of care, in this instance, Department of Veterans Affairs (VA) and Medicare-reimbursed care. These dual users would be inaccurately represented in the analysis if only one source of data were analyzed. Methods: A retrospective analysis of 13 years of nationwide Medicare and VA inpatient and institutional outpatient data beginning with the three years pre-diagnosis (1986–1990) through a minimum of five years post-diagnosis (1994–1998) was conducted. Death data were available through June 2005. Data were also extracted from tumor registry files, Computerized Patient Record System Files, and paper medical records at each VA. The population studied included all VA patients diagnosed with colorectal cancer and surgically treated for cure during the five-year period 1989–1993, who were Medicare-eligible at diagnosis, and survived the index admission. Results: Of the 6612 patients treated with curative intent during the five-year period, 4924 (74%) could be staged. Of these, 4551 (92%) were deemed eligible for the study. Of the eligible patients, 77% were diagnosed with colon cancer and 23 percent with rectal cancer. The majority (89%) had adenocarcinoma. The histopathologic grade was moderately differentiated for 54% and well differentiated for 19%. As of June 2005, 77% had died. Including all stages (0- IV), the average survival in months after treatment was 86 (median=61). Survivorship differed significantly by stage at diagnosis (p < .001). Conclusions: This rich database provides a wealth of data for subgroup analyses of survivorship, recurrence patterns, and health services utilization patterns within and across systems of care. Identifying predictors of survivorship within subgroups of this population is currently under way [Table: see text]

Poster 8: Lens Care and Patient Satisfaction

Local recurrence (LR) after curative therapy for renal cell cancer is a rare event, and surgery is still the primary treatment option.This was a single-institution, single-arm retrospective study from a prospectively conducted database. A total of 91 patients with a median age of 63.0 years (interquartile range, 57.5-68.3), who had undergone LR resection after initial curative treatment of RCC were enrolled. The time to LR (TTLR) was defined as the interval from primary curative surgery to LR. Cancer-specific survival, overall survival, and progression-free survival were evaluated after LR resection. Statistical analyses of the clinical and pathologic variables were performed using Cox regression analysis and the Kaplan-Meier method.The median time to LR was 29.8 months (interquartile range, 10.8-64.3). On multivariate analysis, age > 65 years, T3/T4 stage, Fuhrman grade 3/4, major venous infiltration, and positive surgical margins were related to early LR after primary curative surgery. LR size of ≤ 7 cm and TTLR of > 24 months were associated with longer cancer-specific survival. Furthermore, patients with a TTLR of > 24 months had better overall survival and progression-free survival. Of the entire cohort, intraoperative radiation therapy and targeted therapy were used in 17 (18.7%) and 15 (16.5%) patients, respectively.Advanced age, T3/T4 stage, Fuhrman grade 3 or 4, major venous infiltration, and positive surgical margins at primary tumor resection were related to a greater risk of early LR. An LR size of ≤ 7 cm and TTLR of > 24 months were associated with favorable oncologic outcomes after LR resection. Thus, patients who present with a longer TTLR and smaller LR size, along with favorable features at primary tumor resection, will benefit from surgical treatment.

Long-term survival patterns of a large nationwide cohort of elderly veterans with colorectal cancer

3708 Background: Administrative databases have generally not been designed to permit cancer researchers to readily follow patients forward from the period pre-diagnosis through initial curative intent treatment, adjuvant therapy, post-treatment follow-up, to the final endpoint of either death or loss to follow-up. One major hurdle to cancer research using such databases has been the lack of data such as stage at diagnosis, and histopathologic type and grade. A second major hurdle is that many patients use more than one system of care, in this instance, Department of Veterans Affairs (VA) and Medicare-reimbursed care. These dual users would be inaccurately represented in the analysis if only one source of data were analyzed. Methods: A retrospective analysis of 13 years of nationwide Medicare and VA inpatient and institutional outpatient data beginning with the three years pre-diagnosis (1986–1990) through a minimum of five years post-diagnosis (1994–1998) was conducted. Death data were available through December 2003. Data were also extracted from tumor registry files, Computerized Patient Record System Files, and paper medical records at each VA. The population studied included all VA patients diagnosed with colorectal cancer and surgically treated for cure during the five-year period 1989–1993, who were Medicare-eligible at diagnosis, and survived the index admission. Results: Of the 6612 patients treated with curative intent during the five-year period, 4902 (74%) could be staged. Of these, 4535 (93%) were deemed eligible for the study. Of the eligible patients, 77% were diagnosed with colon cancer and 23 percent with rectal cancer. The majority (88%) had adenocarcinoma. The histopathologic grade was moderately differentiated for 54% and well differentiated for 19%. As of December 2003, 74% had died. Including all stages (0- IV), the average survival in months after treatment was 75 (median=61). Conclusions: This rich database provides a wealth of data for subgroup analyses of survival, recurrence patterns, and particularly, of health services utilization patterns within and across systems of care. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Heartland Division, Department of Veteran's Affairs Medical Center

Long-term survival patterns of a large nationwide cohort of elderly veterans with colorectal cancer

3708 Background: Administrative databases have generally not been designed to permit cancer researchers to readily follow patients forward from the period pre-diagnosis through initial curative intent treatment, adjuvant therapy, post-treatment follow-up, to the final endpoint of either death or loss to follow-up. One major hurdle to cancer research using such databases has been the lack of data such as stage at diagnosis, and histopathologic type and grade. A second major hurdle is that many patients use more than one system of care, in this instance, Department of Veterans Affairs (VA) and Medicare-reimbursed care. These dual users would be inaccurately represented in the analysis if only one source of data were analyzed. Methods: A retrospective analysis of 13 years of nationwide Medicare and VA inpatient and institutional outpatient data beginning with the three years pre-diagnosis (1986–1990) through a minimum of five years post-diagnosis (1994–1998) was conducted. Death data were available through December 2003. Data were also extracted from tumor registry files, Computerized Patient Record System Files, and paper medical records at each VA. The population studied included all VA patients diagnosed with colorectal cancer and surgically treated for cure during the five-year period 1989–1993, who were Medicare-eligible at diagnosis, and survived the index admission. Results: Of the 6612 patients treated with curative intent during the five-year period, 4902 (74%) could be staged. Of these, 4535 (93%) were deemed eligible for the study. Of the eligible patients, 77% were diagnosed with colon cancer and 23 percent with rectal cancer. The majority (88%) had adenocarcinoma. The histopathologic grade was moderately differentiated for 54% and well differentiated for 19%. As of December 2003, 74% had died. Including all stages (0- IV), the average survival in months after treatment was 75 (median=61). Conclusions: This rich database provides a wealth of data for subgroup analyses of survival, recurrence patterns, and particularly, of health services utilization patterns within and across systems of care. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Heartland Division, Department of Veteran's Affairs Medical Center

Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials

Objective: To review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer.Design: Systematic review and meta-analysis of randomised controlled trials of intensive compared...

Malaria chemoprophylaxis with tafenoquine: a randomised study

Tafenoquine is an analogue of primaquine with an improved therapeutic and safety profile. It has a long half-life and activity against liver-stage malaria parasites, so may be useful for chemoprophylaxis. In this randomised, double-blind study we assessed the efficacy and safety of tafenoquine in different doses. 2144 individuals aged 12-20 years living in Lambaréné, Gabon, an endemic area for Plasmodium falciparum malaria, were invited to take part. 535 attended, and 426 eligible participants were randomly assigned tafenoquine (250 mg, 125 mg, 62.5 mg, or 31.25 mg) or placebo daily for 3 days. 417 received initial curative treatment with halofantrine, and 410 completed the assigned prophylaxis regimen. During follow-up of 70 days, adverse events were recorded and thick blood smears were examined weekly. The primary and secondary endpoints were the number of individuals with positive blood smears by day 56 and day 77, respectively. Analyses were per-protocol. Eight positive blood smears were recorded by day 56 (four/82 participants in the placebo group; four/79 tafenoquine 31.25 mg group). By day 77, 34 positive blood smears had been recorded (14/82 placebo; 16/79 tafenoquine 31.25 mg; three/86 tafenoquine 62.5 mg; one/79 tafenoquine 125 mg; none/84 tafenoquine 250 mg). Numbers of adverse events did not differ significantly between the treatment groups. Tafenoquine is effective and well tolerated. It has the potential to replace currently used drugs for malaria chemoprophylaxis.

Randomised placebo-controlled study of atovaquone plus proguanil for malaria prophylaxis in children

The combination of atovaquone and proguanil is highly effective and safe for the treatment of Plasmodium falciparum malaria. We aimed in this randomised, double-blind, placebo-controlled study to assess the efficacy and safety of this combination for malaria prophylaxis. 320 children who lived in a hyperendemic area for P falciparum malaria were stratified by weight and randomly assigned atovaquone plus proguanil or placebo once daily for 12 weeks. All children received initial curative treatment with atovaquone and proguanil before the start of chemosuppression. We recorded adverse events daily and collected thick blood smears once a week. The primary endpoint was a positive blood smear. 25 of 140 children in the placebo group and none of the 125 children in the atovaquone plus proguanil group had positive smears during chemosuppression (p<0.001). Adverse events during the chemosuppression phase did not differ between the groups. The combination of atovaquone plus proguanil is a highly effective and well-tolerated chemosuppressive antimalarial in children. This drug combination could replace current regimens.

Immediate vs. salvage resection after local treatment for early rectal cancer.

There is an increasing awareness of local procedures to treat early stage rectal cancer. Abdominoperineal resection (APR) or low anterior resection (LAR) has been recommended if adverse pathologic findings are encountered in the local excision specimen. No data compare the impact on survival of "immediate" resection for adverse features vs. "salvage" resection for clinical recurrence. We reviewed retrospectively 155 patients who underwent initial curative treatment of invasive rectal cancer by excision (91), snare-cautery (44), and fulguration (20). Twenty-one patients underwent APR/LAR immediately after initial local treatment, whereas another 21 patients underwent salvage APR/LAR for local recurrence. The disease-free survival after APR/LAR was 94.1 percent for the immediate group and 55.5 percent for the delayed group (P < 0.05). This decreased survival observed after delayed resection supports the recommendation for immediate APR/LAR when adverse pathologic features are present in the excision specimen.

A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients.

The principles of dose-response and combination chemotherapy were basic to the design of the initial curative standard-dose treatment regimens for leukemias, lymphomas, and testis cancer. Agents were selected with different dose-limiting toxicities, resulting in subadditive toxicity in combination. A fourth principle in the design of curative regimens was to combine agents with different mechanisms of action to avoid cross-resistance. Based on these principles, combinations of the highest tolerated doses of active noncross-resistant agents are required to decrease the emergence of drug resistance and achieve optimum cytotoxicity. Hematopoietic stem-cell support provides a mechanism for significantly increasing the doses of active agents, a strategy that has resulted in the cure of 10% to 50% of selected patients with lymphoma who could not be cured with standard-dose therapy. The lack of sufficiently effective cytoreductive conditioning regimens remains the major impediment to improving the high-dose therapy of patients with solid tumors. In this study, 27 patients with solid tumors were treated with a combination of cyclophosphamide, thiotepa, and carboplatin (CTCb) in a phase I-II study. Severe mucositis and neurotoxicity were dose-limiting. The maximum-tolerated dose (MTD) of the combination was 6.0 g/m2 of cyclophosphamide, 500 mg/m2 of thiotepa, and 800 mg/m2 of carboplatin. There were two deaths (7%) of sepsis, and an overall response rate of 72% in refractory tumors (81% in breast cancer). CTCb is a combination with low morbidity and high cytoreductive efficacy designed to exploit the principles of curative cancer chemotherapy.

Local control and outcome of patients irradiated for isolated chest wall recurrences of breast cancer

Between January 1970 and December 1978, 149 breast cancer patients with isolated chest wall recurrences developing after initial curative treatment (mastectomy with or without postoperative irradiation) were referred to the University Clinic for Radiotherapy and Radiobiology of Vienna. Following radiotherapy, survival was analysed in 134 patients with regard to the amount of disease in the chest wall at the time of treatment and local tumour control. Patients with "subclinical" disease (after excision of solitary recurrences) had a median survival time of 55 and 50 months for controlled and uncontrolled disease in the entire chest wall, respectively. The corresponding survival times for patients with "macroscopic" chest wall disease was 36 and 25 months, respectively. Local tumour control within the irradiated field was 69% for patients with subclinical disease and 49% for patients with macroscopic tumour manifestation. Freedom from tumours in the entire chest wall could be achieved in 41% of patients with subclinical and 24% of patients with macroscopic disease. The 5-year survival rate for patients with subclinical disease, with tumour control in the entire chest wall is 53%. Of all 134 patients, 22% survived 5 years from the time of local recurrence.

Electrical cardioversion for persistent atrial fibrillation after treatment of thyrotoxicosis.

Summary A review of 22 patients with atrial fibrillation after the treatment of thyrotoxicosis, who underwent elective electrical cardioversion, showed that only 45% were still in sinus rhythm at 2 years and 36% in the long term (mean 7·4 years). There were no significant differences in factors assessed between those persisting in sinus rhythm and in those who relapsed. A delay in the initial curative treatment of thyrotoxicosis may be a factor in influencing the outcome.

Carcinoma of the Maxillary Sinus

A retrospective review of 124 patients of carcinoma of the maxillary sinus treated at Kurume University Hospital from 1971 to 1980 was completed. Of these 124 patients, 111 patients had not been previously treated and underwent curative treatment, 8 patients underwent palliative treatment, and 5 patients were those who had been previously treated at other clinics. The results of this retrospective studies are summarized as follows: 1) In the 58 patients who were followed up for 5 years or more after the onset of initial curative treatment, the 3- and 5-year crude survival rates calculated by direct method were 58.6% and 51.7%, respectively. 2) In the 111 patients who underwent curative treatments, the 3- and 5-year cumulative survival rates calculated by the actuarial method were 61.8% and 52.3%, respectively. 3) Among various factors which can be determined before the treatment, T category and L. V. histological classification were considered to be useful in order to estimate the prognosis. 4) With respect to T categorization, the JJC proposal proved to be better than the A JC proposal. 5) The majority of causes of deaths was uncontrolled primary lesion. Involvement of the cervical lymph nodes were controlled in most cases and distant metastasis were not frequent. 6) As for the treatments, the best modalities appeared to be the following two combinations: (1) infusion, radiation and necrotomy followed by an eradicating surgery and (2) infusion, radiation and necrotomy associated with a mass reduction surgery. 7) Three year crude survival rate calculated by direct method was equally 80.0% in the above two combination therapies. Final conclusions on the comparison between these two Combination treatments await further followup studies of more patients.

Primary extranodal lymphoma: response to treatment and factors influencing prognosis.

The cumulative 10 year lymphoma experience of a teaching hospital and two of its affiliated institutions was reviewed. From this group, a series of 39 cases of regionally localized primary extranodal lymphomas (Ann Arbor Stages IE and IIE) were selected for study. This group of patients was analyzed for response to initial curative treatment and factors influencing prognosis. The disease-free survival rate following initial treatment is 41% and the rate is 51% if those treated for a single relapse are included. Factors which clearly influence prognosis in this group are stage (extent of disease) at presentation and Rappaport histologic subclassification. The relationships of anatomic site and age to prognosis independent of other factors are unclear. There appears to be an association between sites of involvement in Waldeyer's Ring and the gastrointestinal tract seen both initially and in sites of relapse. An analysis of relapse patterns revealed that 33% of relapses occur as solitary extranodal "skip" recurrences that when treated with radical local treatment may result in long disease-free survival. The latter is one of several findings which suggest that a modification of the current Ann Arbor staging system may be necessary to encompass certain unique features of this group of tumors.