 Vol.46 n° 1
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Current Controversies in Cancer: Should Chemotherapy be Used as a Treatment of Advanced Colorectal Carcinoma (ACC) in Patients over 70 Years of Age?
Pro: B. Daniele - Division of Medical Oncology B, National Cancer Institute, via M. Semmola, 80131 Napoli, Italy
Introduction: Chemotherapy of advanced solid tumours in the elderly has long been the subject of controversy. In most advanced cancers of the elderly the limited prolongation of survival, if any, included by chemotherapy is balanced against the increased treatment toxicities which are ussually observed in older patients. Another issue to take into account is the interaction of chemotherapy with management of other comorbid illnesses often present in cancer patients of advanced age.
The size of the problem: Colorectal cancer is the second most common type of cancer after lung cancer in men and breast cancer in women [1]. In 1985, 678.000 new cases of colorectal cancer were diagnosed [2] and 394.000 patients died of the disease [3] worldwide. Approximately 70% of patients with colorectal cancer are over 65 years old [4] and, in Europe, approximately 40% are over 74 years old [5]. Thus, in the future the oncologist will face the question of whether to treat older patients with advanced colorectal cancer (ACC) with increasing frequency.
Contra: P. D. Simmonds L. Y. Best - CRC Wessex Medical Oncology Unit, Southampton General Hospital, Tremona Road, Southampton S016 6YD, U.K.
Introduction: Colorectal cancer is predominantly a disease of the elderly, with of all deaths from this disease occurring in people over the age of 75 years [1]. Furthermore, the number of cases occurring in elderly people is expected to increase in the future as a result of population ageing. The primary treatment of colorectal cancer is surgical resection, but over half of all patients will eventually die of metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis [2].
Although the rate of progression of the disease is very variable, patients with advanced colorectal cancer have a median survival of only 6-9 months from the diagnosis of metastatic disease, during which time they may develop a wide variety of physical and psychological symptoms that detract from their quality of life and frequently precipitate hospital admission [3]. Since advanced colorectal cancer is usually incurable, the aims of treatment are prolongation of survival, effective symptom control and maintenance or improvement of quality of life (QoL). The adverse effects of chemotherapy must be weighed against any gain in survival, or improvement in cancer symptoms, a balance that will also be influenced by the choice of treatment and the expertise of the oncologist and supporting staff in selecting patients and managing side effects [3]. In order to make such a judgement, these outcomes must be known for the patient group to which the treatment is to be offered.
Palliative chemotherapy is now offered to an increasing proportion of patients with advanced colorectal cancer due to recent advances which have resulted in increased response rates, a reduction in the side-effects of therapy and the demonstration of modest survival benefits, but there are good reasons to exercise caution in the use of this treatment in patients over 70 years of age.
Review
The discovery of the Philadelphia chromosome and its consistent involvement in chronic myeloid leukemia (CML) was the first time that a relationship between a cytogenetic abnormality and malignancy was demonstrated. This review will try to provide an insight into the molecular mechanisms underlying this disease and outline the therapeutical options for patients with CML.
Introduction: chronic myeloid leukemia
During the last decades it has become clear that most if not all cancers have a genetic origin.1 One of the most paradigmatic examples is chronic myeloid leukemia (CML). The discovery of the Philadelphia chromosome2 and its consistent involvement in CML3 was the first time that a relationship between a cytogenetic abnormality and malignancy was demonstrated. This review will try to provide an insight into the molecular mechanisms underlying this disease and outline the therapeutical options for patients with CML.
Centre Effect on Treatment Outcome for Patients with Untreated Acute Myelogenous Leukemia? An Analysis of the AML 8A Study of the Leukemia Cooperative Group of the EORTC and GIMEMA
In the AML 8A study patients were treated with remission-induction therapy followed by one consolidation course. Patients in complete remission (CR) were randomised between autologus bone marrow transplantation (ABMT) and a second intensive consolidation course, except for those with a histocompatible sibling donor, who received allogeneic bone marrow transplantation (alloBMT). This analysis was performed to determine whether centers which only performed induction and consolidation therapy, achieved similar results as centers who also performed transplantation. 542/676 (80%) from transplantation centers and 150/194 (77%) from referring centers achieved CR, with an early death rate of 5% and 11%, respectively (P=0.01). 66% of patients with a donor from transplantation centers received alloBMT in first CR compared with 57% from referring centers (P=0.02). Transplantation centers randomised 64% of patients without a donor, referring centers 47% (P=0.04). The full protocol treatment was completed by 275/542 (51%) and 61/150 (41%) patients, respectively (P=0.04). The overall survival rate at 6 years from diagnosis was 34% and 36%, respectively (P=0.9). In conclusion, the type of the centre did not appear to have an influence on overall survival. The feasibility of the study was acceptable for both types centres. The referring centres applied more selection for transplantation. Depite a more intensive second-line treatment and transplantation centres, the over-all outcome remained similar to that of referring centers.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial)
The EMA86 study showed efficacy of intensive sequential chemotherapy with mitoxantrone, 12mg/m² day on days 1-3, etoposide, 200mg/m²/day as a continuous infusion on days 8-10 and cytarabine (araC), 500 mg/m²/day as continuous infusion on days 1-3 and 8-10 (EMA regimen) in previously treated patients with AML. The goal of the EMA91 study was to determine whether administration of GM-CSF between the two sequences of EMA chemotherapy and during the second sequence could increase therapeutic efficacy by potentially increasing leukemic cell recruitment into the S phase of cell cycle before the second sequence. One hundred and ninety-two patients aged less than 65 years with previously treated AML received GM-CSF, 5 mg/kg/day or placebo from day 4 to day 8 of EMA chemotherapy. One hundred and twenty were refractory and 72 were in first relapse after a complete remission (CR) of more than 6 months duration. CR rates after one course of chemotherapy were 65% in the GM-CSF group (refractory: 51%; fist relapse: 89%), not significantly different from the 59% CR rate (refractory: 46%; fist relapse: 81%) in placebo group. Median time to recovery of neutrophils was 38 and 37 days and median time to last platelet transfusion 32 and 32 days respectively in the GM-CSF and placebo groups. Who grade ³ 3 non-hematologic toxicities were mainly sepsis (45% AND 51%, respectively) and mucositis (34% and 31%) and did not differ between the two groups. Toxic death rate was 5% and 8%, respectively, in the GM-CSF and placebo groups. Patients achieving CR were scheduled to receive six courses of maintenance with reduced-dose EMA. Time to progression tended to be longer in the GM-CSF group (median 154 vs 115 days, progression-free rate at 18 months 33% vs 19%, P=0.08), particularly in refractory patients (P=0.06). However, at the current follow-up, this did not translate into a insignificantly longer disease-free survival and survival. Cell cycle studies showed increased recruitment of cells in the S phase between day 4 and day 8 in the GM-CSF group compared to placebo (P=0.006). However, this did not significantly relate to prognosis in this cohort of patients. GM-CSF might marginally increase efficacy of sequential chemotherapy without increasing its toxicity in the absence of any detected relationship between this effect and observed leukemic cell recruitment into the cell cycle.
Local Therapy and Other Factors Influencing Site of Relapse in Patients with Localised Ewing's Sarcoma
Relapse patterns have been documented in 191 children with localised Ewing's sarcoma treated with the United Kingdom Children's Cancer Group (UKCCSG) Ewing's Tumour regimen ET2. All received chemotherapy comprising ifosfamide, vincristine, doxorubicin and actinomycin D. Local treatment modality was excision and or radiotherapy depending on tumor site and response to primary chemotherapy. Although not strictly comparable, due to the clinical indications used for each modality, local relapse rates were very low and were similar, irrespective of the type of local treatment modality: radiotherapy (3/56), surgery (7/114) or a combination (0/20). Combined relapse (local+distant) rates were similarly low irrespective of the type of local therapy: radiotherapy (4/56), surgery (4/114) or a combination (0/20). Overall survival was lower in females (P=<0.04), older children (P=<0.002) and those with primaries at sites other than long bones (P=<0.02). It is concluded that with effective intensive chemotherapy combined with either radiotherapy or surgery, local control in this study was excellent at sites other than the pelvis. Preventing distant relapse, pre-dominantly to lung and bone, remains the major challenge.
Quality of Life Instruments in Oncology
The objective of this article is to aid clinicians in understanding the current state of the development and application of quality of life (QOL) instruments as outcome measures in cancer clinical research and practice. As a result of the achievements of the past two decades, the concept of QOL has been defined and many reliable and valid measurement tools have been developed. The two main approaches to QOL assessment, psychometric-based and utility-based, are discussed together with a brief description of the strategies for meaningful interpretation of QOL profiles. QOL measures in oncology have the potential to be used to study populations in randomised clinical trials, to aid patient-clinician interactions in routine practice and to support policy decision making and economic evaluation of healthcare provision.
Current Controversies in Cancer -
Is Postoperative Irradiation after Radical Prostatectomy Necessary?
Pro: H. Van Poppel, L. Vanuytsel, Z. Petrovich and L. Baert
Introduction
In the past two decades in the European Community and the U.S.A there has been a sharp increase in the number of patients diagnosed with adenocarcinoma of the prostate (CaP) and an increase in the proportion of patients diagnosed with capsule confined tumours (1). At the same time, major improvements in surgical techniques resulted in a higher probability of tumour control, improved survival and a better quality of life of treated patients (2-4). The 5-year survival rates for caucasian CaP patients in U.S.A in the early 1980s (1). These factors helped to increase the acceptance of radical prostatectomy to become the most widely applied definitive therapy for patients with localised CaP. This increase in the incidence of the use of radical prostatectomy is apparent for all age groups and is particularly high (70%) in younger (<55 years of age) patients (5).
Since the routine use of prostate specific antigen (PSA) after surgery, it has become obvious that complete tumour eradication is less commonly achieved than expected. Indeed, in spite of major advances in prostatic imaging modalities and the use of PSA, accurate preoperative staging remains an elusive goal (6). In some published reports, over 50% of radical prostatectomy patients have pathological evidence of extracapsular tumour spread or the presence of positive surgical margins (7). The presence of pT3 disease iss of major importance since most of these patients eventually have a local recurrence or systemic disease manifested most frequently by PSA elevation (8).
The most important factor responsible for treatment failure is the underestimation of the primary tumour, which although clinically locally confined, proves to be extraprostatic on pathological examination (9). Local failure can lead to recurrent local tumour that can be responsible for progression and death. Distant spread can also be present at the time of surgery without being recognised. In both situations, one could find a rationale for adjuvant treatment, but the indication for adjuvant therapy after radical prostatectomy on the basis of the pathology of the resected specimen remains controversial. Whereas the presence of distant disease usually indicates the institution of systemic therapy, the presence of suspected localised persistent disease presents a therapeutic dilemma (10).
Irinotecan in Second-line Treatment of Metastatic Colorectal Cancer: Improved Survival and Cost-effect Compared with Infusional 5-FU
In a recent multicentre, randomised, controlled, open-label study (Rougier and colleagues, Lancet 1998, 352, 1407-1412), irinotecan significantly increased survival without any deterioration in quality of life compared with best-estimated infusional 5-fluorouracil (5-FU) therapy in the setting of second-line treatment for metastatic colorectal cancer. The aim of the cost-effectiveness analysis reported here was to compare the economic implications, from a U.K. perspective, of replacing 5-FU therapy [either as a single agent (Lokich regimen, B2) or in combination with folinic acid (de Gramont regimen, B1, or AIO regimen, B3)] with irinotecan as second-line therapy for metastatic colorectal cancer. Resource utilisation data collected prospectively during the study, supplemented by both a questionnaire to investigators and local expert clinical opinion, were used as a basis for estimating cumulative drug dosage, chemotherapy administration and treatment of complications. Drug acquisition costs were derived from the British National Formulary (March 1998), and unit costs for clinical consultation and services were derived from relevant 1996/1997 cost databases. Although cumulative drug acquisition costs per patient were higher with irinotecan than with infusional 5-FU therapy, these were at least partially offset by lower cumulative costs per patient associated with administration of therapy and treatment of complications in the irinotecan arm than in the 5-FU arm. Based on the incremental costs per life year gained (LYG), irinotecan was considered to be cost-effective by commonly accepted criteria compared with either the B1 or B2 regimens. Irinotecan was cost-saving compared with the B3 regimen (that is significant survival gain and a reduction in costs). Thus, not only is there strong evidence for the use of irinotecan as standard second-line therapy in metastatic colorectal cancer, but the results of this prospective economic evaluation have shown that irinotecan also represents sgood value for money in this clinical setting.
Cancer Chemoprevention: Progress and Promise
Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. The focus of chemoprevention research in the next millennium will include defining the genotypic and phenotypic (functional and histological) changes during carcinogenesis, the cancer risk conferred by these changes, their modulation in preclinical experimentation and randomised clinical trials by chemopreventive drugs, dietary agents and regimens and treatments resulting from early detection. The key elements of this research effort will be basic and translational risk evaluation programmes; chemopreventive and dietary agent drug discovery and development; development of transgenic animal models; required safety and pharmacology studies; well-designed phase I, II and III chemoprevention studies; and much expanded early detection programmes. The large number of chemoprevention research programmes now ongoing ensures that the promise of chemoprevention will continue to be realised in the next decade.
Tamoxifen in High-risk Premenopausal Women with Primary, Breast Cancer Receiving Adjuvant Chemotherapy.
Following modified radical mastectomy, pre- and perimenopausal (amenorrhoea for <5 years) patients with stage II or III breast cancer received CMF (cyclophosphamide 600, methotrexate 40, 5-fluorouracil 600 mg/m² intravenously (i.v.) every 4 weeks, 9 cycles). The effect on recurrence-free survival (RFS) and overall survival (OS) of the addition of adjuvant tamoxifen (TAM) to adjuvant chemotherapy was examined by randomisation either to no additional treatment (n=314), or concurrently TAM 30mg daily for 1 year (n=320). 40% had positive, 12% negative and 48% unknown receptor status. One year after surgery 21% ersus 35% (CMF + TAM versus CMF) were still menstruating (P<0.01). With a median follow-up of 12.1 years there was no difference in RFS (10-year RFS 34% versus 35%, P=0,81) or OS (45% versus 46%, P=0.73). In a Cox proportional hazards model, tumour size, number of metastatic lymph nodes, frequency of metastatic nodes in relation to total number of nodes removed, degree of anaplasia, age, and menostasia within the first year after operation were significant independent prognostic factors for RFS, and the same factors except age for OS. No significant interactions with TAM were seen. Thus, in this group of pre- and perimenopausal highrisk early breast cancer patients with heterogeneous receptor status given CMF i.v., concurrent TAM for 1 year did not improve the outcome. These results do not exclude that receptor positive patients may benefit from adjuvant TAM for longer periods given sequentially to chemotherapy.
Risk factors for local recurrence after breast-conserving therapy
Background. Breast-conserving therapy has been widely accepted as a standard treatment for early breast cancer both in Western countries and in Japan. In Western countries, many studies have investigated the risk factors for local recurrence after breast-conserving therapy (BCT), but few such studies have been done in Japan.
Methods. To determine the risk factors for local recurrence in 399 breast cancer patients (stage I and II, n=396; stage III, n=3) who had undergone BCT with or without postoperative radiation therapy, we evaluated their clinico-pathological features by univariate and multivariate analyses. The patients were treated at Osaka National Hospital between February 1988 and December 1997.
Results. Univariate analysis showed that a young age (£ 45 years; P = 0.0005) was a significant risk factor for local recurrence, while radiation therapy (P = 0.0058) and adjuvant endocrine therapy (P = 0.0041) significantly reduced the risk of local recurrence. In patients with BCT, without radiation therapy a positive surgical margin significantly increased the risk of local recurrence (P = 0.0470). Multivariate analysis showed that a young age (P = 0.02285) was a significant independent risk factor for local recurrence, while radiation therapy (P = 0.0457) significantly decreased recurrence. In patients with a negative surgical margin, radiation therapy (P = 0.0158) and adjuvant endocrine therapy (P = 0.0421) significantly reduced the relative risk of local recurrence, to 0.160 and 0.366, respectively. In patients with a positive surgical margin, radiation therapy marginally significantly (P = 0.0756) reduced the relative risk of local recurrence, to 0.181, and adjuvant endocrine therapy significantly (P = 0.0119) reduced the risk, to 0.076.
Conclusions. Young, age and lack of radiation therapy or adjuvant endocrine therapy were risk factors for local recurrence in breast cancer patients treated with breast-conserving therapy, with surgical margin status also being a possible risk factor.
Influence of psychological response on survival in breast cancer: a population-based cohort study
Background. The psychological response to breast cancer, such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease, has been suggested as a prognostic factor with an influence on survival. We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer.
Methods. 578 women with early-stage breast cancer were enrolled in a prospective survival study. Psychological response was measured by the mental adjustment to cancer (MAC) scale, the Couortauld emotional control (CEC) scale, and the hospital anxiety and depression (HAD) scale 4-12 weeks and 12 months after diagnosis. The women were followed up for at least 5 years. Cox's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response, with adjustment for known clinical factors associated with survival.
Findings. At 5 years, 395 women were alive and without relapse, 50 were alive with relapse, and 133 had died. There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression (hazard ratio 3.59 [95% CI 1.39-9.224]). There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category (1.55 [1.07-2.25]). There were no significant results found for the category of "fighting spirit".
Interpretation. For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect. A high score for depression is linked to a significantly reduced chance of survival; however, this result is based on a small number of patients and should be in interpreted with caution.
Paediatric Update
PAEDIATRIC HODGKIN's Disease (HD) is an outstanding example for a paediatric malignancy, which can now be cured in the vast majority of children, without a significant risk of adverse side-effects, mostly achieved by combination treatment. The evolution of staging and treatment strategies have been based on the progress in diagnostic imaging as well as in planning and performance of radiotherapy. Treatment strategies have been increasingly tailored to the individual risk of relapse. The therapeutic ratio can be improved by reducing the burden of each treatment modality, which results in avoidance of major side-effects. These strategies, developed for paediatric HD, have recently even become an example for strategies to be studied in adult HD. Deeper insight into the molecular process of HD now allows a better understanding of the malignant transformation process.
Primary CNS lymphoma: Treatment with Combined chemotherapy and radiotherapy
Primary central nervous system lymphoma (PCNSL) is a relatively uncommon primary brain tumor, but it has become the focus of many clinical trials because of its rising incidence and unique sensitivity to systemic chemotherapeutic agents. Radiotherapy can achieve high response rates and remissions in most patients, but survival is usually only 12-18 months because disease recurs. The addition of systemic chemotherapy, particularly intravenous methotrexate, had markedly improved disease control and many patients can achieve a durable remission and occasionally cure of their disease. Conventional systemic lymphoma drug combinations such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are ineffective. High-dose methotrexate is the single most active and important agent in the treatment of this disease. Whether improved disease control can be accomplished by adding other drugs to high-dose methotrexate or whether it is sufficient as a single agent has yet to be answered. High-dose methotrexate combined with cranial irradiation yields a median survival of at least 40 months and five year survival rates of 22%. However, neurotoxicity is substantial in a significant proportion of patients, particularly those over the age of 60 at the time of treatment. As many as 50% of such patients develop severe dementia. This is particularly important in a disease where approximately half of patients above the age of 60 had presentation. Efforts are now being directed towards not only improving disease control but also minimizing late neurotoxicity. Most efforts are currently directed towards using chemotherapy as the sole modality in the treatment of PCNSL, but both an optimal chemotherapy regimen, and the role of radiotherapy remain to be determined.
Radiotherapy in the treatment of primary central nervous system lymphoma (PCNSL)
The use is radiotherapy alone to treat primary central nervous system lymphoma (PCNSL) does not produce the high local control and survival rates that it does in limited extranodal non-Hodgkin's lymphoma outside the central nervous system CNS). Even with doses of whole brain radiation therapy (WBRT) to 40 + 20 Gy boost, the Radiation Therapy Oncology Group (RTOG) reported a local control rate of 39%. Seventy-nine percent of recurrences were in the 60 Gy region. The median survival was 11.6 months. This response to local radiotherapy is quite different from the response of non-CNS Diffuse Large Cell Lymphoma where doses of 30-40 and >40 Gy have a 75-90% local control rate. Neither systemic lymphoma nor PCNSL have a classic radiotherapy does response. For PCNSL there appears to be a threshold dose that ranges in the literature between 30 and £ 50 Gy with a median of 40 Gy. Therefore, when radiotherapy is combined with chemotherapy that crosses the BBB, WBRT and/or boost doses may be able to be decreased, especially in patients achieving a complete response. Promising data from the Centre Leon Berard suggest that this is possible. When such chemotherapy was combined with intrathecal chemotherapy and 20 GY WBRT, they obtained a 56% actuarial 5 year survival rate. Confirmation of single institution reports of favorable results such as these are needed. Cooperative group and intergroup trials are needed to define optimal therapy.
Primary central nervous system lymphoma: From clinical presentation to diagnosis
Immunocompetent patients with primary central nervous system lymphoma (PCNSL) present with a median age of 55 years, immunosupressed patients with a median age of 40 years. They show a broad range of signs and symptoms. Symptoms of increased intracranial pressure and personality change are most frequent, followed in frequency by ataxia and hemiparesis. The median time from onset of symptoms to diagnosis is 3-5 months in immunocompetent patients and 2 months in immunodeficient patients. The time to diagnosis can be considerably longer in patients with slowly developing personality change or fluctuating symptoms due to spontaneous or steroid-induced remission of so-called sentinel lesions. Native CT scans show isso- or hyperdense lesions with homogenous contrast enhancement. T1-weighted MRI scans show hypointense and T2-weighted scans hyperintense lesions. The definitive diagnosis of PCNSL requires biopsy. In some cases, however, the definitive diagnosis may exclusively be made by the demonstration of malignant B-lymphocytes in the cerebrospinal fluid.
FIGO Stage IIIC Endometrial Carcinoma with Metastases - Confined to Pelvic Lymph Nodes: Analysis of Treatment Outcomes, Prognostic Variables, and Failure Patterns Following Adjuvant Radiation Therapy
Objectives. This study was undertaken to evaluate the prognostic significance of isolated positive pelvic lymph nodes on survival and to analyze other prognostic variables, overall survival, and failure patterns in surgically staged endometrial carcinoma patients with positive pelvic lymph nodes and negative para-aortic lymph nodes following radiation therapy (RT).
Methods. Between January 1, 1987, and December 31, 1997, 782 women underwent primary treatment for uterine cancer at Indiana University Medical Center. Through a review of the medical records, we identified 58 patients with pathologic stage IIIA, 27 patients with pathologic stage IIIB, and 77 patients with pathologic stage IIIC endometrial carcinoma. Patients with pathologically positive or unsampled para-aortic lymph nodes and patients who received preoperative radiation therapy were excluded, leaving a study group of 17 patients with nodal metastases confined to pelvic lymph nodes. Thirteen patients received adjuvant pelvic RT using AP-PA or four-field technique. A median dose of 5050 cGy was delivered. Four patients received whole abdominal irradiation (WAI) delivering a median dose of 3000 cGy. Two patients received vaginal cuff boosts of 1000 and 3560 cGy to 0.5 cm from the vaginal surface mucosa via Cs-137 brachytherapy. Two patients also received adjuvant chemotherapy (cis-platinum and doxorubicin) and/or hormonal therapy (megestrol acetate). Disease-free and overall survivals were estimated using the Kaplan-Meier method of statistical analysis and prognostic variables were analyzed using the log-rank test.
Results. With a median follow-up of 51 months the actuarial 5-year disease-free survival was 81% and the actuarial 2-year and 5-year overall survival rates were 81 and 72%, respectively. Univariate analysis revealed that positive peritoneal cytology in conjunction with positive pelvic lymph nodes imparts a greater risk of recurrence and decreased overall survival. There were no pelvic and/or upper abdominal failures, but there were recurrences in the para-aortic lymph nodes (two patients) and distantly (two patients).
Conclusion. Surgery followed by postoperative pelvic RT is a viable treatment option for pathologically staged stage IIIC endometrial carcinoma with disease confined to the pelvic lymph nodes. Failures in the para-aortic region suggest a possible role for extended-field RT. Patients with positive peritoneal cytology in conjunction with nodal metastasis fared poorly with pelvic RT. Studies evaluating the efficacy of WAI are ongoing. Finally, substages within FIGO stage IIIC are recommended in an effort to better understand and define treatment strategies which might be appropriate for these patients.
The Use of Adjuvant Radiation Therapy by Members of the Society of Gynecologic Oncologists
Objective: The aim of this study was to determine the attitudes of the members of the Society of Gynecologic Oncologists with respect to the use of adjuvant radiation therapy in women with endometrial cancer.
Methods: An anonymous survey concerning the use of adjuvant radiation therapy in endometrial cancer was mailed to all members of the Society of Gynecologic Oncologists listed in the 1998 directory.
Results: Of the 767 listed members, 325 (42%) returned completed surveys. Less than 20% of respondents recommended adjuvant radiation therapy in stage IA grade 1 or 2 and stage IB grade 1 endometrial cancer. Adjuvant radiation is recommended by 40 to 50% of respondents in women with stage IA grade 3 and IB grade 2 tumors. Most recommend adjuvant radiation for all women with >50% myometrial invasion or grade 3 tumors with any myometrial invasion. Lymph node sampling is attempted in all cases by 48% of respondents. For those familiar with Gynecologic Oncology Group (GOG) Study No. 99, 20% stated that they were more likely to recommend adjuvant radiation and 27% stated that they were less likely to recommend adjuvant radiation based on the preliminary results. Except in stage IA grade 1 tumors, the chance of recommending further therapy in women with all stages and grades was significantly less if a complete staging procedure including lymph node dissection had been performed.
Conclusions: Complete staging appears to decrease the chance that postoperative therapy will be recommended. The use of adjuvant radiation therapy seem to have declined slightly as a result of GOG Study no. 99. Future studies in women with endometrial cancer that do not require lymph node sampling should evaluate the frequency of adjuvant therapy in the absence of complete staging.
Whole Abdominal Radiotherapy Following Second-Look Laparatomy for Ovarian Carcinoma
Aim: The safety and efficacy of whole abdominal radiotherapy was evaluated as salvage or consolidation treatment for ovarian cancer patients treated with primary surgery and chemotherapy, followed by second-look laparatomy (SLL). Overall survival and acute and late toxicity of treated patients were assessed.
Methods: Patients were recruited between April 1981 and June 1994. All patients had SLL performed at Royal Prince Alfred Hospital after completion of primary chemotherapy. Data collected included demographic details, diagnosis, tumor stage, histology, grade, adjuvant chemotherapy, and radiotherapy. Radiation dose and fractionation, field size, boost volume and dose, failure to complete treatment and treatment interruptions, renal dose, and acute and late toxicity were recorded.
Results: Fifty-one patients were evaluated; the median age was 51 years. Median follow-up for patients still alive was 62 months. Prior to 1988, chemotherapy comprised oral chlorambucil, with or without cisplatin (n = 25), while after this date all patients (n = 26) received primary cisplatin-based therapy. A radiation dose of 22.5 Gy over 22 fractions was planned to the whole abdomen followed by a pelvic boost of 22 Gy in 11 fractions. Radiotherapy was completed in 37 (73%) patients. Treatment interruptions were necessary in 12 (24%) patients. Thrombocytopenia, neutropenia, nausea, vomiting, and diarrhea were the main causes of incomplete or interrupted treatment. Late bowel toxicity was seen in 6 (12%) patients, 2 of whom required laparotomy to relieve obstruction. There were no treatment-related deaths. Seven of the 51 patients are alive and free of disease, 2 died from other causes, and 2 are alive with evidence of recurrent or progressive disease. Mean follow-up time for surviving patients is 78.5 months. Overall survival at 2,5, and 10 years was 65, 27, and 10%, respectively. Residual disease after primary surgery, smaller preirradiation tumor residuum, and completion of radiotherapy were independently associated with improved overall survival.
Conclusion: In this poor-prognosis group of patients, a combined approach of surgery, chemotherapy, and radiotherapy, while associated with acceptable toxicity, may not afford a prolongation of survival.
REVIEW ARTICLE
Lymphoma can often present in unusual situations. This article provides a comprehensive review of the literature in which both non-Hodgkin's lymphoma and Hodgkin's disease are discussed.
The clinician involved in treating lymphoma should never be surprised about unusual presentations. One of the major fascinations of this disease is its protean manifestations. The literature abounds with single case reports and small series of patients with lymphoma occurring at uncommon sites, and to do the topic justice would require a book rather than a review article. To prepare a review article thus requires selectivity and author bias. Needless to say, many articles will not be referenced, and to the authors, apologies are offered. The review will attempt to cover all major organ systems and where possible include recent articles and reviews that cover this broad field.
Up date in the management of advanced ovarian carcinoma
Cytoreductive surgery followed by platinum-based chemotherapy represents the standard therapeutic strategy for the management of patients with advanced ovarian carcinoma [1,2]. Current regimens are able to induce an objective response in 60-80% and a pathological complete response in 25-30% of cases [3-15]. The achievement of a pathological complete response has a favourable prognostic relevance; however, a review of the literature shows that 19.5-71% of complete responders develop recurrent disease after a median time of 14-32 months from second-look [16-23]. According to the International Federation of Gynecology and Obstetrics (FIGO) Annual Report 1998, the 5-year survival rate is 41.1% in stage IIIa, 24.9% in stage IIIb, 23.4% in stage IIIc and 11.1% in stage IV [24].
Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer
This randomized study was designed to determine the response rates, survival and toxicities of single-agent gemcitabine (GEMZARTM) and a combination of cisplatin/etoposide in chemonaive patients with non-resectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Gemcitabine 1000 mg/m² was given as a 30-min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplating 100 mg/m² on day 1, and etoposide 100 mg/m² on days 1 (following cisplatin, 2 and 3. Major eligibility criteria included histologically confirmed non-small cell lung cancer, measurable disease, Zubrod performance status 0-2, no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. One hundred and forty-seven patients were enrolled, 72 in the gemcitabine and 75 in the cisplatin/etoposide arm. Patient characteristics were well-matched across both arms. Sixty-seven gemcitabine and 72 cisplatin/etoposide patients were qualified for efficacy analysis. There were no complete responses, but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response rates of 17.9% (95% CI: 9.6-29.2%) and 15.3% (95% CI: 7.9-25.7%), respectively. Median survival times were 6.6 months (95% CI: 4.9-7.3 months) for gemcitabine and 7.6 months (95% CUL 5.4-9.3 months) for cisplatin/etoposide. The 1-year survival probability estimate was 26% for gemcitabine and 24% for cisplatin/etoposide. There were no statistically significant between-group differences in time-to-event measures, but patients in the gemcitabine arm had a greater probability of achieving a tumour response after 2 months (probability estimate: 8 vs. 0%) and of the response lasting at least 6 months (73 vs. 45%). Clinical and haematologic toxicity was more pronounced in the cisplatin/etoposide arm. Quality-of-life measures indicated a significant worsening of symptomatology in the cisplatin/etoposide arm for hair loss, nausea and vomiting, and appetite loss. This randomized study provides further evidence that single-agent gemcitabine is na active and effective therapy for patients with non-resectable, locally advanced or metastatic NSCLC and good performance status, and that it is better tolerated than the combination cisplatin/etoposide.
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Revista Brasileira de Cancerologia - Volume 46 n°1 Jan/Fev/Mar 2000