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A review of the role of established tumour markers.

Increasing numbers of commercial assays for the established tumour markers are available which are capable of excellent analytical performance. Whilst all these assays are useful as research tools, their clinical value is more limited and should be appreciated before any decision is taken to offer a tumour marker assay service. 1. Calcitonin (medullary carcinoma of thyroid), alphafetoprotein (hepatoma) and human chorionic gonadotrophin (choriocarcinoma) are the only tumour markers that can be used for screening for malignancy in high risk populations. 2. Hormones, paraproteins, alphafetoprotein, human chorionic gonadotrophin and prostate specific antigen are valuable in establishing the diagnosis of certain tumour types. 3. Alphafetoprotein and human chorionic gonadotrophin concentrations at the time of diagnosis are of value in predicting prognosis in specific tumour types. 4. Although their sensitivity for a particular tumour type may be poor, most tumour markers can be used for monitoring the therapy and follow-up of selected marker positive patients. Optimal clinical results of the management of patients with malignancy are usually obtained by specialist centres, and laboratory tumour marker services should be established so that they are appropriate to local oncology specialities.

Biomarkers, Tumor↗

Possible synergy of radiotherapy and chemo-immunotherapy in metastatic renal cell carcinoma (RCC).

PURPOSE: Bone metastases or local recurrences are widely viewed as poor prognostic signs for successful immunotherapy for metastatic renal cell carcinoma (RCC), and even partial remission is a rarity. We assessed the efficacy of the combination of radio and chemo-immunotherapy for bone metastases or local recurrences form RCC. MATERIALS AND METHODS: From February 1994 until September 1997 twelve patients with progressive renal cell carcinoma (9 with bone metastases and 3 with local recurrence) were treated with a combination of chemo-immunotherapy and radio therapy. RESULTS: Four out of twelve patients achieved complete remission (CR), one patient had a partial remission (PR), three were stable and four had disease progression under radio therapy and chemo-immunotherapy. Yet three pts. died of the disease. The toxicity symptoms according to WHO ranged between grade 2 and grade 3. CONCLUSION: Our data suggest that the combination of radio therapy and chemo-immunotherapy may induce a synergistic antitumor effect for the treatment of bone metastases or local recurrences from renal cell carcinoma.

Adult↗

Experimental surgery on the Cloudman S91 melanoma with the carbon-dioxide laser.

The continuous wave CO2 laser lacks a number of draw-backs of the pulsed Ruby laser, and seems attractive for tumor surgery. We compared the CO2 laser with conventional surgery in experiments on mice bearing the Cloudman S91 melanoma. We had the same rate of local recurrence and lung metastasis in both techniques.

Animals↗

[Adjuvant radiotherapy of rectal cancer].

Evaluation and refinement of surgical techniques in rectal carcinoma have reduced the rate of local recurrences. Nevertheless recurrence it remains high at more than 20% in patients with extensive infiltration of perirectal tissues and cures are an exception. Overview of many years of experience with adjuvant radiotherapy shows that local recurrence rate can be reduced and survival the rate improved.

Combined Modality Therapy↗

[Cause and surgical management of local recurrence of rectal cancer following radical resection retaining the anus].

Of seventy-one patients with rectal cancer after radical resection retaining the anus, 15 developed local recurrence with a recurrence rate of 21.1%. Local recurrence was correlated with improper safety margin from the lower edge of cancer to the anal end. There was statistical significant difference between 3 cm or more and 2 cm or less. The local recurrence was also related to the pathologic stage, histologic differentiation and implant of free cancer cells. It is suggested that the surgical indication of saving the anus be strict and without stretching, the safety margin from the lower edge of cancer to the anal end should not be less than 2 cm in early rectal cancer and not less than 4 cm in advanced lesions. During the operation, no touching tumor technique, thorough rinsing of the peritoneal cavity and pre- or post-operative radiotherapy are important for prevention of local recurrence. Early local recurrent rectal cancer can be detected by periodic examinations.

Adenocarcinoma↗

[Prognostic factors in local recurrence rate after surgical therapy of rectal carcinomas].

From January 01, 1985 to December 31, 1993 515 patients with primary rectal cancer underwent operative treatment at the hospital of general and abdominal surgery of the university of Mainz. In 294 patients with conventional surgical treatment and R0-resection of the tumor we investigated the influence of tumor-, patient- and therapeutic factors on local tumor recurrence. At a univariate analysis the following factors were significant: UICC-staging (p = 0.001), pT-classification (p = 0.001), pN-classification (p = 0.013) and localisation of the tumor (p = 0.013). These results could be verified for the pT-classification and pN-classification in a multivariate analysis. The significant influence of operative treatment (p = 0.034), blood transfusion (p = 0.018) and preoperative raised CEA (p = 0.026) depended on significant differences of UICC - staging and tumor - localisation of the different groups. Grading, sex and age had no influence. Inspite of a shift of local resurrence from 13% to 50% (0% to 42.9% for resections, respectively 6.7% to 55.4% for exstirpations) we could not find a significant influence of the surgeon. This fact depended on the dividing of a small number of cases on a lot of surgeons. In our opinion the influence of the surgeon or of different hospitals on local recurrence should be investigated in further studies.

Blood Transfusion↗

Local excision of rectal cancer: review of literature.

In selected patients, local excision of rectal cancer may be an alternative to radical surgery such as abdominoperineal excision of the rectum or anterior resection. Local excision carries lower mortality and morbidity, without the functional disturbance or alteration in body image that can be associated with radical surgery. There are several techniques of local therapy for rectal cancer, with most experience being available in transanal excision. Transanal endoscopic microsurgery is also used but experience with this newer technique is limited. Patient selection is the most important factor in successful local excision, however specific criteria for selecting patients have not been universally accepted. Review of the published literature is difficult because of the variation in adjuvant therapy regimes and follow-up strategies, as well as results reported in terms of local recurrence and survival rates. There is increasing evidence to suggest that local excision should be restricted to patients with T1 stage rectal cancer without high-risk factors. The place for local excision in patients with T2 or high-risk T1 tumours requires prospective, randomised multi-centre trials comparing radical surgery with local excision, with or without adjuvant therapy.

Chemotherapy, Adjuvant↗

The melanotic neuroectodermal tumor of infancy. Report of two cases and review of the literature.

The melanotic neuroectodermal tumor of infancy (MNTI) is a rare childhood neoplasm with an alarming but classical clinical presentation. It appears as a rapidly enlarging mass in the jaws of skull of infants and unless MNTI is considered in the differential diagnosis, the lesion can easily be mistaken for a malignant neoplasm. Although possessing an aggressive growth rate and radiographic appearance, the MNTI almost always behaves in a benign fashion and can be treated with local excision. However, recent reports of malignant behavior as well as of occasional recurrences make close follow-up important. Approximately 139 cases of the MNTI have been reviewed and tabulated with respect to age at discovery, sex, tumor location, length of follow-up, and whether recurrence occurred, 2 additional cases, 1 of which was in the mandible, are presented along with theories of origin and recommended therapy.

Diagnosis, Differential↗

Postoperative radiotherapy for stage pT3 carcinoma of the prostate: improved local control.

PURPOSE: We determined whether radiotherapy after radical prostatectomy leads to improved results in patients with stage pT3 carcinoma of the prostate. MATERIALS AND METHODS: In a prospective nonrandomized study of 203 patients with clinical stage T2 prostate cancer treated with radical prostatectomy 88 underwent surgery alone, 89 received early postoperative radiotherapy generally because of pathological stage T3 disease and 26 received delayed radiotherapy for local recurrence. The disease was stage pT3N0/X in 135 patients. RESULTS: For patients with pathological stage T3 cancer actuarial local recurrence rates were significantly decreased in the early postoperative radiotherapy group compared to the surgery only group (p = 0.005), while actuarial metastatic rates (p = 0.6) and cause specific survival rates (p = 0.04) were not significantly different. Multivariate analysis for all patients in both groups identified adverse features of increased postoperative prostate specific antigen levels, seminal vesicle involvement, lack of postoperative radiotherapy and positive lymph nodes. Late toxicity was severe (Radiation Therapy Oncology Group grade 3 or 4) in 13 surgery only and 17 early postoperative radiotherapy group patients. Of those who were potent postoperatively the incidence of impotence in the early postoperative radiotherapy group was 89% compared to 59% in the surgery only group (p = 0.003). For patients treated with delayed radiation for clinical local recurrence the actuarial local control rate was 54% after 10 years. CONCLUSIONS: Local radiotherapy appears to improve local control of stage pT3 cancer but has no impact on overall survival.

Actuarial Analysis↗

Renal salvage procedures in patients with synchronous bilateral Wilms' tumors: a report from the National Wilms' Tumor Study Group.

Synchronous bilateral Wilms' tumor accounts for 4% to 6% of all Wilms' tumors. Renal salvage procedures (partial nephrectomy and enucleation) have been recommended to conserve renal parenchyma. The objective of this study was to review the results of renal salvage operations performed in children who had bilateral neoplasms. The authors reviewed the records of 98 children enrolled in the Fourth National Wilms' Tumor Study who had synchronous bilateral tumors and underwent renal salvage procedures. One hundred thirty-four kidneys were managed with renal salvage procedures. Complete excision of gross disease was accomplished in 118 (88%) of the 134 kidneys. Local tumor recurrence in the remnant kidney or tumor bed occurred in 11 cases (8.2%). Overall, 72% of the kidneys were preserved, and the 4-year survival rate was 81.7%. The surgical morbidity after a salvage procedure was comparable to that of a complete nephrectomy in patients with unilateral Wilms' tumor. Although the incidence of positive surgical margins is worrisome, it did not invariably lead to local recurrence in the remnant kidney or the tumor bed.

Biopsy↗

[Testicular tumors. Mortality and recurrence after inadequate therapy].

From 1983 to 1994, 293 patients with testicular germ cell tumors were treated at the Department of Urology, Bonn University, Germany. 252 patients (86%) were available for follow-up studies. 17/252 (6.8%) of patients died of disease, 41/252 (16%) had a tumor recurrence after complete remission. 20/41 (49%) patients with recurrence, who mainly had been referred for further treatment, had been treated inadequately. Inadequate treatment consisted of surgical failures after orchiectomy, incomplete retroperitoneal lymph node dissection after chemotherapy, delay of treatment, and inadequate chemotherapy. 80% of recurrences were found within the first two years after treatment, late relapses were found in 3.6%. Early recurrences were mainly pulmonary, late recurrences mostly occurred in the retroperitoneum or atypical. 20% of all recurrences were local recurrences.

Adult↗

Conservative therapy of breast cancer in Queensland.

PURPOSE: Primary radiation therapy following breast-conserving surgery has been an accepted alternative to mastectomy in Europe and North America for many years. In Australia, however, the history of breast conservation for early invasive breast cancer is much shorter. The purpose of this study was to evaluate the results of breast conservation in a state-wide Australian radiotherapy service. METHODS AND MATERIALS: Between January 1982 and December 1989, 512 patients were treated with primary radiation therapy after breast conserving surgery. This analysis is based on a review of these patients, all of whom had Stage I or II breast cancer. RESULTS: With a median follow-up of 50 months, the 5-year actuarial rate of overall survival was 84% and disease-free survival was 80%. There have been 22 isolated local recurrences in the breast. The time to an isolated breast recurrence ranged from 12 to 83 months (median, 26 months). The 5-year actuarial rate of an isolated breast recurrence was 4%. The recurrence rate was higher for patients with involved margins (15% vs. 2%, p < 0.01). Local recurrence was also more likely in the presence of extensive ductal carcinoma in situ (DCIS), as opposed to no extensive DCIS (10% vs. 2%, p < 0.01). CONCLUSION: These results affirm that primary radiation therapy after breast conserving surgery in Queensland, has been given with a low rate of local recurrence, comparable to that obtained in other centers.

Actuarial Analysis↗

Effect of delay in initiating radiotherapy for patients with early stage breast cancer.

AIMS: For early stage breast cancer, a standard treatment option is partial mastectomy followed by radiation treatment. The 5-year risk of local recurrence ranges from 6-9%. Variable waiting times for radiation treatment of breast cancer in our institution provided an opportunity to evaluate the impact of waiting time on the risk of local recurrence. MATERIALS AND METHODS: Between January 1988 and December 1989, 482 patients with stage I and II breast cancer were treated with radiotherapy in our institution. Information on prognostic factors, such as age, tumour size, histological grade, number of positive lymph nodes and margins of resection, was abstracted from their charts. The interval between date of surgery and date of initial radiation treatment was noted. Dates of local recurrence, metastasis and deaths were recorded. RESULTS: At 5 years, the local recurrence rate was 8%, the metastatic rate 12% and the 'cause-specific' survival rate 90%. In univariate analysis, the risk of local recurrence was associated with younger age, higher histological grade and time to radiation treatment. In the multivariate analysis, the effect of time to radiation treatment on the risk of local recurrence was equivocal. CONCLUSION: Delay in radiation treatment may be associated with an increased risk of local recurrence of breast cancer, at least in our centre. Future research is needed on a larger data set to more accurately estimate the effect of time to radiation treatment on the risk of local recurrence.

Adult↗

Calculated volume of prostate cancer identifies patients with clinical stage T1C disease at high risk of biochemical recurrence after radical prostatectomy: a preliminary study.

OBJECTIVES: To evaluate whether the calculated volume of prostate cancer (cVca) in patients with clinical Stage T1c prostate cancer who were treated surgically was a good predictor of biochemical disease-free prostate-specific antigen (PSA) recurrence. METHODS: Between 1990 and 1996, patients with prostate cancer who were surgically treated for clinical Stage T1c at Brigham and Women's Hospital were retrospectively evaluated, and 188 patients (median PSA 6.9 ng/mL) were included in this study. cVca (determined by cancer-specific PSA, prostate volume, and Gleason grade), pathologic stage, and time to PSA failure were assessed. RESULTS: cVca correlated strongly with the preoperative PSA level (P <0.00001, chi-square test), Gleason grade (P <0.00001), and pathologic stage (P <0.00001). Kaplan-Meier curves for PSA disease-free survival were constructed for patients with cVca less than 0.5 cm(3) (group 1), cVca of 0.5 to 4.0 cm(3) (group 2), and cVca greater than 4.0 cm(3) (group 3). The 2-year PSA disease-free survival rate was 100%, 81%, and 36% for groups 1, 2, and 3, respectively (P <0.0001). Cox multiple regression analysis demonstrated that cVca was superior to PSA and Gleason score for determination of serologic PSA failure after surgery. CONCLUSIONS: Our results demonstrated that cVca is a good predictor of biochemical recurrence in patients with clinical Stage T1c prostate cancer. Perhaps, after validation by others, cVca can serve as a tool in choosing various treatment options for prostate cancer.

Chi-Square Distribution↗

Evaluation of bone scan as a screening work-up in primary and local-regional recurrence of breast cancer.

To evaluate the use of radionuclide bone scan in staging patients with primary and local-regional recurrence of breast cancer, we reviewed the results in 265 patients with primary breast cancer who had the scan either preoperatively or within 6 weeks of surgery, and in 39 patients presenting with their first local-regional recurrence. All patients were clinically staged according to the revised 1983 criteria of the American Joint Committee for Cancer Staging and End-Results Reporting. None of the 92 with stage I and four of 95 patients with stage II had a positive scan. Eleven of 41 with stage IIIA and 13 of 37 with stage IIIB had a positive bone scan. In patients with their first local-regional recurrence, 12 of 39 had a positive scan. Follow-up scans were available in 61 patients with clinical stage I and II breast cancer who had adjuvant chemotherapy for pathological involvement of axillary node. There were six conversions observed in 61 scans obtained during the first year. Seven converted in follow-up scans in 47 patients in the second year. We conclude that although bone scans have a low positive yield in stage I and II breast cancer, their use in the preoperative setting and in the follow-up of patients with axillary node involvement detects early converters. Bone scans are justified in stage IIIA and IIIB breast cancer and in patients being evaluated for local-regional recurrence.

Adult↗

Analysis of local recurrence after breast conservative treatment for invasive breast cancer: a single institution cohort.

In a group of 900 patients treated for carcinoma of the breast, we evaluated patient-, tumour- and treatment-related parameters, predicting the success or failure of conservative treatment for invasive breast cancer. Thirty-one patients developed local recurrences which were detected within 0.1-12.1 years after treatment of the primary tumour (with a median of 6.2 years), providing a risk of 2% at 5 years and 9% at 10 years. The locally recurrent tumours and their original primary tumours of 28 patients could be retrieved from the pathology laboratory archives. These 28 tumours of the recurrence group (RG) were matched with tumours without local recurrence, the non-recurrence group, for age at time of diagnosis, duration of follow-up and T- and N-stage. The tumours were studied for type and grade of invasive tumour including the in situ component and involvement of surgical margins. In addition, the expression of cell-cycle proteins, p53, Ki-67 (MIB-1) and BCL-1, as well as HER-2/ neu oncoprotein, estrogen and progesterone receptor were investigated. We found a mean age at diagnosis for the RG of 50 years, and the mean age at time of diagnosis for the whole group of 900 patients was 56 years (p=0.003). Thirty-nine percent of the RG had a positive surgical margin, which was the case for only 18% in the control group (p=0.09). The presence of the in situ component was also correlated with increased local recurrence (p=0.022). Furthermore, local recurrence was also associated with a significantly increased occurrence of distant metastases (p=0.001). We conclude that breast conservative treatment is safe with a low local recurrence rate.

Age of Onset↗