Phase II study of neoadjuvant paclitaxel and cisplatin for operable and locally advanced breast cancer: analysis of 126 patients.

In an earlier study, we have demonstrated a high clinical and pathologic response rate of neoadjuvant paclitaxel (P) and cisplatin (C) for patients with locally advanced breast cancer (LABC). The current phase II study includes larger number of patients who had longer follow-up. A total of 126 consecutive patients with noninflammatory LABC (T2 >4 cm, T3 or T4, N0-N3, M0) were included in the study. Patients were scheduled to receive three to four cycles of the neoadjuvant PC (paclitaxel 135 mg m(-2) and cisplatin 75 mg m(-2) on day 1) every 21 days. Patients were then subjected to surgery and subsequently received six cycles of FAC (5-fluorouracil 500 mg m(-2), doxorubicin 50 mg m(-2), and cyclophosphamide 500 mg m(-2)) or four cycles of AC (doxorubicin 60 mg m(-2) and cyclophosphamide 600 mg m(-2)); all drugs were administered intravenously on day 1 with cycles repeated every 21 days. Patients then received radiation therapy, and those with hormone receptor-positive tumours were given adjuvant tamoxifen intended for 5 years. The median age was 41 years. Clinically, 12, 52, and 37% of patients had T2 >4 cm, T3, and T4, respectively. The mean tumour size was 7 cm (95% CI, 7.3-8.5). The clinical nodal status was N0, N1, and N2-N3 in 32, 52, and 17% of patients, respectively. Disease stage at diagnosis was IIA (2%), IIB (32%), IIIA (28%), and IIIB (39%). Clinical assessment of the primary tumour and the axillary nodal status after primary chemotherapy showed that 35 patients (28%) achieved complete response (cCR), while 80 (63%) demonstrated partial response to PC. Of patients with evaluable pathologic data of the primary tumour (123 patients), complete pathologic response (pCR) was achieved in 29 patients (24%), and an additional nine (7%) only had a microinvasive disease. Moreover, 20 of the 122 patients (16%) had no residual disease in the primary tumour or in the axillary nodes. Failure to attain cCR predicted failure to achieve pCR. At a median follow-up of 37.5 months (95% CI, 31.5-43.3), 71% were alive with no recurrence, 16% were alive with evidence of disease, and 13% were dead. Of the 122 patients who had surgery, 36 (29%) developed recurrence including one of the patients who attained pCR. The median overall or disease-free survival has not been reached with a projected 5-year overall survival (OS) and disease-free survival (DFS) of 85% (+/-4%) and 63% (+/-5%), respectively. On multivariate analysis, clinical response of the primary tumour, pathological response of the primary tumour, and the pathological nodal status were identified as independent prognostic variables for DFS. No variable, however, was identified to prognosticate OS. PC was acceptably safe. Neoadjuvant PC as used in this phase II study in a multidisciplinary strategy was highly effective. Clinical and pathologic responses remain the most important variables that predict outcome.

Extramedullary myeloid cell tumours localised to the mediastinum: a rare clinicopathological entity with unique karyotypic features.

Extramedullary myeloid cell tumour (EMMT) localised to the mediastinum is a rare manifestation of acute myeloid leukaemia, forming less than 4% of all cases of EMMT. In contrast to other types of EMMT, cytogenetic characteristics of this rare entity are relatively unknown. This report describes a patient with EMMT who had evidence of superior vena cava syndrome and normal peripheral blood counts at diagnosis. The results from an initial biopsy specimen were consistent with a diagnosis of mediastinal large B cell lymphoma. A diagnosis of acute myeloid leukaemia was made three months after initial diagnosis by bone marrow examination. Review of the initial biopsy specimen showed strong positivity for myeloperoxidase, revealing that the patient had been initially misdiagnosed as having large B cell lymphoma. Cytogenetic studies revealed a near triploid and near tetraploid karyotype with structural abnormalities in 12 and three metaphases, respectively. Review of the literature showed that a near tetraploid or triploid karyotype is found in most of the reported cases of mediastinal EMMT. Thus, the presence of a near triploid/tetraploid karyotype and mediastinal EMMT may represent a specific subset of EMMT. The biological relevance of this observation is discussed.

Localized non-Hodgkin's lymphoma of Waldeyer's ring: clinical features, management, and prognosis of 130 adult patients.

BACKGROUND: Waldeyer's ring (WR) is the primary site of non-Hodgkin's lymphoma (NHL) involvement in approximately 5% to 10% of all lymphoma patients, and it accounts for more than half of all primary extranodal lymphomas of the head and neck. Materials and Methods A retrospective review was performed of 130 adult patients with localized (stages I and II) WR-NHL seen at a single institution over 18 years. RESULTS: Patients had a median age of 55 years, and the male-female ratio was 1:5:1. Seventy five (58%), 46 (35%), and 9 (7%) patients had primary tonsillar, nasopharyngeal, and base of the tongue lymphoma, respectively. Forty-five (35%) and 85 (65%) had stage I and stage II disease, respectively. Most patients (109 patients, 84%) had diffuse large B-cell NHL (DLC). Chemotherapy (CT) was given to 58 (45%) patients, whereas 26 (20%) received radiation therapy (RTX), and 46 (35%) were managed with a combination of chemotherapy and radiotherapy (CMT). One hundred nine (84%), 16 (12%), and 5 (4%) patients attained complete remission (CR), partial remission (PR), and treatment failure, respectively, with no difference in CR rates between the three therapeutic modalities. Of those patients with DLC, 90 (83%), 15 (14%), and 4 (3%) demonstrated CR, PR, and treatment failure, respectively. In a multivariate analysis, the modified International Prognostic Index (IPI) was found to predict the attainment of CR. Over a median follow-up of 49 months; 76 (58%) of the patients were alive and disease-free, 5 (4%) were alive with evidence of disease, and the remaining 49 (38%) were dead. Most distant relapses were in nongastrointestinal extranodal sites. The median overall survival (OS) has not been reached; however, the projected 5-year OS was 58%. No OS difference was noted between patients with stage I and stage II. Cox proportional hazards model identified primary tonsillar site and a low-risk group as defined by the modified IPI were associated with favorable OS. The median event-free survival was 82.3 months, with the primary tonsillar site, and low-risk modified IPI group were associated with favorable EFS in a multivariate analysis. Probably because of the high frequency of patients with DLC, the outcome and the prognostic factors in those patients were not distinctive from those for the whole group. The CMT was not associated with a superior OS compared with either of the single modality treatments; however, it was associated with more favorable EFS. CONCLUSIONS: This series characterized the clinicopathologic features and outcome of adult patients with early stage WR-NHLs. No survival difference was noted between stage I and stage II, and the outcome was favorable. Primary tonsillar site and the low-risk group of the modified IPI predicted favorable OS and EFS. CMT is probably superior to single modality treatment; however, prospective studies are warranted.

Primary intestinal diffuse large B-cell non-Hodgkin's lymphoma: clinical features, management, and prognosis of 66 patients.

BACKGROUND: In Saudi Arabia, primary gastrointestinal non-Hodgkin's lymphoma (NHL) is common. Recently we have reported one of the largest series of primary gastric (PG) diffuse large B-cell lymphoma (DLCL). This has prompted the analysis of another series of patients with primary intestinal DLCL to depict the clinical features and the outcome of that disease and to compare those with that for PG involvement. PATIENTS AND METHODS: The data of 66 adult patients with primary intestinal NHL having DLCL histology were retrospectively reviewed. RESULTS: Patients had a median age of 45 years. Of 64 treated patients, 16% and 84%, received single and multiple modality treatment, respectively. Seventy-six percent, ten percent, and fourteen percent attained complete remission (CR), partial remission (PR), and no response/progressive disease, respectively. Multivariate analysis failed to identify any variable that predict the likelihood of attaining CR. Over a median follow-up of 81 months for all 66 patients, 32 (48%) were alive and disease-free, 5 (8%) were alive with evidence of disease, and the remaining 29 (44%) were dead. The median overall survival (OS) was 101 months and it was 58% (+/- 6%) and 48% (+/- 7%) at 5- and 10-year, respectively. Of the 54 patients who achieved CR or PR, the median event-free survival (EFS) was not reached, but the predicted 5- and 10-year EFS was 61% (+/- 7%) and 52% (+/- 7%), respectively. Only low serum albumin (<30 g/l) was associated with adverse OS and EFS in a univariate analysis, however, multivariate analysis was not possible. Our analysis showed that compared with single-modality management, multi-modality strategy attained significantly higher CR, and advantageous EFS, but without a significant superior effect on OS. In comparison with patients with PG DLCL, those with primary intestinal disease demonstrated more adverse prognostic features, but had an equivalent survival. CONCLUSIONS: This series characterized the clinico-pathologic features and outcome of patients with primary intestinal DLCL. While surgical resection in primary intestinal NHL seems beneficial, only prospective randomized studies can ascertain its precise role. Compared with patients with PG NHL, patients with primary intestinal disease had more prevalence of adverse prognostic features.

High complete pathological response in locally advanced breast cancer using paclitaxel and cisplatin.

BACKGROUND: In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). METHODS: A total of 72 consecutive patients with non-inflammatory LABC (T2 > or = 4 cm, T3 or T4, N0-N2, M0). Patients were scheduled to receive 3-4 cycles of the neoadjuvant PC (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) or 4 cycles of AC (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. RESULTS: The median age was 39 years (range, 24-78). Clinically, 7%, 58%, and 35% of patients had T2 > or = 4 cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (+/- 3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (+/- SE) of 90% (+/- 4%). The median progression-free survival (PFS) was 42.1 (+/- 4.8) months with a projected PFS of 74% +/- 7% at 3-years (for 68 patients). CONCLUSIONS: PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.

Primary gastrointestinal cancers in the Western Region of Saudi Arabia. Is the pattern changing?

OBJECTIVE: To determine the age, sex and relative frequencies of various gastrointestinal malignancies in patients registered with the National Cancer Registry from the Western Region of Saudi Arabia from January 1994 till December 1997, and compare this data with previous hospital based studies about the pattern of these malignancies in Saudi Arabia. METHODS: A National Cancer Registry was established in Saudi Arabia in 1992, and since 1st January 1994 all cancer cases in Saudi Arabia have been registered with the National Cancer Registry. All National Cancer Registry data on patients with primary gastrointestinal cancers from the Western Region of Saudi Arabia from January 1994 till December 1997 was retrieved and analyzed according to ethnic origin, site, age, sex and relative frequencies of various tumors. RESULTS: Out of a total of 1833 cases with primary gastrointestinal malignancies 1207 (66%) were Saudis, while the rest were Non-Saudis. Colorectal cancer was the the most common malignancy found in both population groups accounting for 28.5% of cases in Saudis and 36% in Non-Saudis. Malignancies of liver, stomach and esophagus followed in decreasing frequencies. The mean age of the Saudi population was 58+16 years (standard deviation) with male to female ratio of 1.67:1. About 80% of the patients were above 40 years of age and the peak of onset for most of the tumors was between 50 and 70 years of age. CONCLUSIONS: This study highlights that colorectal cancer is the most common gastrointestinal malignancy seen in the Western Region of Saudi Arabia followed by hepatocellular carcinoma. This is in sharp contrast to the previous hospital based studies from Saudi Arabia and national trends as seen in the cancer incidence report from the National Cancer Registry of Saudi Arabia. The factors for this changing pattern of gastrointestinal malignancy remain to the determined.

Primary gastric non-Hodgkin's lymphoma: clinical features, management, and prognosis of 185 patients with diffuse large B-cell lymphoma.

BACKGROUND: Primary gastric non-Hodgkin's lymphoma (PG-NHL) is common in Saudi Arabia. This has prompted the analysis of a large series of patients with PG-NHL having high-grade diffuse large B-cell lymphoma (DLCL) in order to define the clinical features and outcome of this disease. PATIENTS AND METHODS: The data of all adult patients in the series with PG-NHL having DLCL histology were retrospectively reviewed. Patients were eligible if they had biopsy-confirmed diagnoses obtained by endoscopy or following laparotomy. RESULTS: Over a 16-year period, 185 patients with DLCL PG-NHL were identified and their data were reviewed. Patients had a median age of 54 years. In 53% of them only one initial therapeutic modality was given, while 47% were managed by a multi-modality approach. One hundred forty patients (76%), 19 (10%), and 26 (14%) attained complete remission (CR), partial remission, and no response/progressive disease, respectively. Multivariate analysis showed that poor performance status and advanced stage were negatively associated with the likelihood of attaining CR. Over a median follow-up of 54 months, 118 (64%) of the patients were alive and disease-free, 17 (9%) were alive with evidence of disease, and the remaining 50 (27%) were dead. The projected 5-year and 10-year overall survivals (OS) (+/- SD) were 68% (+/- 4%) and 61% (+/- 6%), respectively. The Cox proportional hazards model identified the same variables of response as adverse prognostic factors of survival. Using the influence of performance status, and stage, a prognostic index was constructed to recognize three prognostically distinctive risk categories with overall survival proportions of 87%, 61%, and 45%, respectively. The unadjusted International Prognostic Index, however, failed to classify patients into prognostically meaningful risk strata. Of the 140 patients who achieved CR, the median disease-free survival (DFS) was not reached, but the predicted 5- and 10-year DFS were 82% and 75%, respectively. A multivariate analysis identified poor performance status as the only independent prognostic covariate that adversely influenced DFS. Our analysis showed that compared with single-modality management, multi-modality strategy attained significantly higher CR, and advantageous OS and DFS. CONCLUSIONS: This large series characterized the clinico-pathologic features and outcome of patients with DLCL PG-NHL. Performance status, and stage significantly influenced patient outcome. A prognostic index was developed and it identified three prognostically distinctive risk groups; however, prospective validation is warranted.

Adult acute myeloblastic leukemia: Experience at King Khalid University Hospital.

BACKGROUND: The clinical features of acute myeloblastic leukemia (AML) and its response to therapy in adult patients in Saudi Arabia are not well defined, as only scanty data has been available. This situation will likely continue unless experience with AML is reported from different institutions in the Kingdom. PATIENTS AND METHODS: In this retrospective study, the records of 52 adult patients with previously untreated de novo acute myeloblastic leukemia (AML) who were treated at King Khalid University Hospital over a five-year period from January 1989 to December 1993 according to the conventional â3+7â regimen were reviewed. The clinical features of the disease, response to therapy and treatment-related complications were identified. RESULTS: There were 33 males and 19 females with a mean age of 30+/-13 years (mean+/-SD). M 4 and M 5 AML were the predominant French-American-British (FAB) subtypes encountered. Sixty-five percent of patients achieved complete remission (CR). The median duration of the first CR of all analyzable patients was 32 weeks. The median CR duration and survival of patients achieving complete remission who survived through their consolidation treatment was 36 and 49 weeks, respectively. CONCLUSION: Both median duration of the first complete remission and survival compare unfavorably with those reported in the literature despite a comparable remission rate. Infectious complications were frequent and accounted for a significant number of mortalities.

Pattern of primary gastrointestinal cancer: King Khalid University Hospital experience and review of published national data.

This study is based on data collected from a total of 629 patients (435 male and 194 female) with histoligically confirmed cancer of the primary gastrointestinal tract and its accessory glands, seen at King Khalid University Hospital (KKUH) between January 1985 and December 1993. During this period, a total of 2464 cancer cases were identified at KKUH. The relative frequency and rank of order are determined for various gastrointestinal cancers, as well as distribution according to age, sex and primary site affected. Gastrointestinal malignancy accounts for 25.5% of total cancer cases seen at KKUH. The mean age of patients was 59 +/- 17 years, with a male-to-female ratio 2.24:1. Primary liver cancer was the most common malignancy (34%), followed by gastric cancer (18%), colorectal (17%) and esophageal cancer (12%). We compared our finding with national published data from different provinces in Saudi Arabia. Results from this report stress the importance of prevention, screening and early detection for gastrointestinal malignancy.

Correlation of fundus lesions and hematologic findings in leukemic retinopathy.

This prospective study evaluated the relationship between the fundus findings in leukemic retinopathy and hematologic parameters. Seventy-four newly diagnosed consecutive patients with acute leukemia were included, 49 with acute myelocytic leukemia (AML), and 25 acute lymphocytic leukemia (ALL). Blood parameters were based on data obtained before starting any therapeutic modalities. Leukemic retinopathy was detected in 32 patients (43%). Patients with ALL and retinal hemorrhages had significantly lower hemoglobin and hematocrit levels than those without hemorrhages (p = 0.004 and 0.018 respectively). AML patients with white-centered hemorrhages had a significantly higher leukocyte count than those without (p = 0.0002). ALL patients with cotton-wool spots had significantly lower hemoglobin levels and hematocrit than patients without such lesions (p = 0.044 and 0.05 respectively). AML patients with cotton wool spots had significantly lower leukocyte and platelet counts than those without (p = 0.019 and 0.003 respectively). Our results suggest that anemia is related to the findings of retinal hemorrhage and cotton-wool spots in ALL patients, that high leukocyte count is associated with white centered hemorrhage in AML patients, and that thrombocytopenia is not associated with retinal hemorrhage in this group of patients.

Granulocyte-Macrophage Colony-Stimulating Factor in Newly Diagnosed Adult Patients with Acute Lymphoblastic Leukemia Treated with Conventional Chemotherapy.

Twenty consecutive adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) were treated with conventional therapy consisting of daunorubicin, vincristine, prednisone and L-asparaginase in standard doses. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered at a single subcutaneous daily dose of 5 microgram per kilogram body weight for fourteen days starting on day 7 of chemotherapy. Twenty two adult patients with acute lymphoblastic leukemia and similar risk characteristics who received the same chemotherapeutic regimen without GM-CSF served as a historical control group. The complete remission rate and the rate of early mortality were similar in both groups of patients. Patients treated with GM-CSF showed significantly faster neutrophil recovery above 0.5 × 10(9)/L than the control patients (P < 0.005). The incidence of febrile episodes and the rate of documented infection were similar in the two groups of patients.

Ceftazidime and amikacin as empiric treatment of febrile episodes in neutropenic patients in Saudi Arabia.

Sixty-four consecutive febrile episodes in 50 consecutive patients with malignancy and neutropenia were empirically treated with a combination of ceftazidime and amikacin. Of 52 analysable episodes, the response rate was 59.6% overall and 26.3% of episodes with microbiologically documented infections with septicaemia. Infection-related death occurred in 10 patients (19.2% of episodes). The response rates were similar in patients with acute leukaemia or other malignancies. Poor response is attributed to increased frequency of infections with Gram-positive and fungal organisms. A modified empiric regimen including cover for Gram-positive and fungal organisms is suggested in similar patient populations.

Pernicious anemia in Saudi Arabs.

Over a five-year period extending from January 1986 to December 1990, seven cases of pernicious anemia in Saudi patients were diagnosed at King Khalid University Hospital in Riyadh. There were five males and two females. The age range was 45 to 73 with a mean age of 61 years. The presenting symptoms, laboratory features and the disease pattern were similar to those described in northern European patients with the possible exception of male predominance in our patients. One patient demonstrated an interesting phenomenon of masking the macrocytosis of pernicious anemia by concurrent beta thalassemia minor. No association with any other autoimmune diseases was detected in any of our patients.

Superior vena caval obstrution: King Khalid University Hospital experience.

A five year experience in 21 patients with superior vena caval obstruction (SVCO) was reviwed. SVCO was due to benign conditions in four patients (19%) and malignant tumors in 17 patients (81%). Lymphoma and lung cancer were the most common causes encountered. The most common symptoms and signs were facial swelling, shortness of breath, jugular venous distention, swelling of face and arms, and engorgement of thoracic veins. Benign disorders had a longer duration of symptoms before presentation and required longer time to make the diagnosis than in malignant disorders. No serious complications resulted from the superior vena cava obstruction itself or the investigate procedures leading to the diagnosis. Prognosis and response to treatment were dependent on the underlying cause of SVCO. Chemotherapy was effective in induction of complete regression of SVCO in the majority of patients with underlying malignant disorders. We conclude that SVCO should be approached invasively for diagnosis and tissue diagnosis of the underlying disorder should dictate the appropriate therapy.

Cancer at king khalid university hospital, riyadh.

This study is based on data collected from a total of 1196 patients (725 males and 471 females) with histologically confirmed cancer seen in King Khalid University Hospital over a 5-year period between September 1985 to August 1990. Four hundred forty-five patients were non-Saudi (37.20%). The relative frequency and rank of order are determined for various cancers in Saudi patients and total group and compared with the results of the other published studies on cancer epidemiology in Saudi Arabia. The most common cancers among Saudi males were liver, non-Hodgkin's lymphomas, stomach, lung, central nervous system, prostate, lymphoid, leukemias, myeloid leukemias, urinary bladder and Hodgkin's lymphomas, central nervous cancers among Saudi females were breast, thyroid, non-Hodgkin's lymphomas, central nervous system, stomach, myeloid leukemias, esophagus, lymphoid leukemias, liver and ovary. Rank order and relative frequency for liver cancer in both sexes is the highest among any study previously published on the epidemiology of cancer in Saudi Arabia.

Spontaneous pneumothorax in metastatic choriocarcinoma.

We report a case of spontaneous bilateral pneumothoraces due to metastatic choriocarcinoma. The patient was successfully treated with tube thoracostomy and chemotherapy. Pneumothorax as a complication of choriocarcinoma has not been reported previously.