Cancer Research and Treatment

Clinical Prognostic Factors and Treatment Outcome of Aggressive Non-Hodgkin's Lymphoma in Elderly Patients: Jung Hye Choi, Myung Ju Ahn, Mo Ran Ki, Ho Suk Oh, Young Yuel Lee, Il Young Choi, In Soon Kim; Cancer Res Treat. 2001;33(4):324-328. Published online August 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.4.324

PURPOSE
The aim of this study was to determine the prognostic factors and treatment outcome of for elderly patients (age>or=60 at time of diagnosis) with aggressive non-Hodgkin's lymphoma (NHL).
MATERIALS AND METHODS
We analyzed 52 patients diagnosed with aggressive NHL between January 1990 and May 2000.
RESULTS
The patient's median age was 69 years (range: 60~92). Thirty-two (61.5%) patients were male. Patients included those with diffuse large B cell (53.8%), peripheral T cell (23.1%), AILD-like T-cell (3.8%), angiocentric (3.8%), mantle cell (3.8%), Burkitt's lymphoma (3.8%), and others (7.9%). International prognostic index (IPI) parameters were as follows: elevated LDH (60.8%), ECOG performance status>or=2 (32.7%), advanced stage (III/IV, 62.7%), and extranodal site>or=2 (11.5%). Twenty-six (50.0%) patients demonstrated a high and high-intermediate IPI. The median follow-up for surviving patients was 26.6 months. The overall median survival was 22.7 months and the 2-year survival rate was 46.9%. Among the 49 patientstreated with chemotherapy, 28 (57.1%) patients achieved complete remission (CR). Univariate analysis identified 8 prognostic factors for overall survival: age<70 (P=0.04), low/low-intermediate IPI (P=0.02), good performance (P= 0.04), normal WBC (P=0.008), normal Hb (P=0.02), normal LDH (P=0.04), CR on first line therapy (P<0.001), and absence of B symptom (P=0.001). In the multivariate analysis, the independent prognostic factors for improved overall survival were age <70 (P=0.03), low/low-intermediate IPI (P=0.03), normal WBC (P=0.006), and CR on first line therapy (P<0.001).
CONCLUSION
In our experience, even elderly patients (>or=60 years) with aggressive NHL can be successfully treated with conventional chemotherapy and the important prognostic factors for survival are age, IPI, initial WBC, and CR on first line treatment.

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Raluca Morar, Norberth-Istvan Varga, Delia Ioana Horhat, Ion Cristian Mot, Nicolae Constantin Balica, Alina-Andree Tischer, Monica Susan, Razvan Susan, Diana Luisa Lighezan, Rodica Anamaria Negrean
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Reduced Dose Intensity FOLFOX-4 as First Line Palliative Chemotherapy in Elderly Patients with Advanced Colorectal Cancer
Jee Hyun Kim, Do-Youn Oh, Yu Jung Kim, Sae Won Han, In-Sil Choi, Dong-Wan Kim, Seock-Ah Im, Tae-You Kim, Jong-Seok Lee, Dae-Seog Heo, Yung-Jue Bang, Noe Kyeong Kim
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Doxorubicin‐based chemotherapy for diffuse large B‐cell lymphoma in elderly patients
Keun‐Wook Lee, Dae‐Young Kim, Tak Yun, Dong‐Wan Kim, Tae‐You Kim, Sung‐Soo Yoon, Dae Seog Heo, Yung‐Jue Bang, Seonyang Park, Byoung Kook Kim, Noe Kyeong Kim
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Results of Treatment with ProMACE - CytaBOM Regimen for Aggressive Non - Hodgkins Lymphoma: Wan Kyu Eo; J Korean Cancer Assoc. 2000;32(1):168-177.

Abstract PDF: PURPOSE
Despite intensive search for the optimal combination chemotherapy for aggres- sive non-Hodgkins lymphoma (NHL), the CHOP regimen is still the standard therapy. We investigated the clinical efficacy of ProMACE-CytaBOM, a third generation regimen, in patients with advanced aggressive NHL.
MATERIALS AND METHODS
We prospectively analyzed the therapeutic approach and the outcome in 33 patients with previously untreated aggressive NHL enrolled into the protocol from June 1994 to June 1997.
RESULTS
Objective response was achieved in 93.9% of the patients. Complete response (CR) and partial response were 54.5% and 39.4%, respectively. The mean time to CR was 75.4 days. CR rate was significantly lower in patients aged 50 years or more (31.3% vs 76.5%, p=0.009). Five year overall (OS) and failure-free survival (FFS) rate were 56.1% and 47.2%, respectively. The age, attainment of CR, and mean relative dose intensity influenced OS significantly (p=0.002, p=0.005 and p=0.039, respectively). The age and attainment of CR influenced FFS significantly (p=0.001 and p=0.003, respec- tively). In patients aged 50 or more, mean relative dose intensity of less than 72% was more frequent than younger age group (73.3% vs 33.3%, p=0.003). There was one toxic death (3.0%).
CONCLUSION
The survival rate of present study was similar to that of previously report concerning ProMACE-CytaBOM. The outcome of elderly NHL patients was poor, and dose intensity may be correlated with the outcome.

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Primary Malignant Lymphoma of the Epididymis: A case report of involvement by diffuse large B cell lymphoma: Mi Ja Lee, Keun Hong Kee; J Korean Cancer Assoc. 1998;30(5):990-996.

Abstract PDF: Isolated involvement of the epididymis by malignant lymphoma is very rare and almost invariably is associated with lymphoma in the adjacent testis. To date, there are four case reports of primary epididymal lymphoma. In this case, 74-year-old man presented with a 3 cm, painless left epididymal swelling. Extensive staging work-up showed no evidence of extraepididymal spread. The epididymectomy was performed. The enlarged epididymis was firm and entirely replaced by whitish gray homogenous tumor measuring 1.8x0.9 cm. Microscopically, the tumor revealed an interductal, highly cellular infiltration, distorting the normal epididymal architecture. The lymphomatous infiltrate was polymorphic, though the predominant cell type exhibited a large irregular and vesicular nucleus. In many areas, small reactive lymphocytes, eosinophils, and occasional plasma cells were interspersed among the neoplastic cell population. Mitoses were frequent. The small lymphoid cells focally infiltrate through the wall of some tubules and small veins. A variable pattern of sclerosis was present throughout much of the tumor. Also there were non-specific granulomas. Immunohistochemical staining revealed that the large cel1s were B cells (CD20 positive) and conclusively lambda light chain restriction. The smaller reactive lymphoid cells were composed of a mixture of B cells and T cells (CD3, UCHL-1 positive). The DNA analysis of lymphoma shows a diploidy DNA content. S phase fraction is 21%. To date, the patient, who treated with chemotheraphy, remains well 9 months after diagnosis. Most lymphomas of testis and epididymis occur in older men, have an intermediate or high grade, diffuse histology, disseminate early, and follow an aggressive clinical course. This case is some similar to the conventional most lymphomas of testis and epididymis. But unusual fetures included that the tumor showed only confined to the epididymis and marked sclerosis.

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Subtypes of Epstein - Barr Virus in Malignant Lymphoma in Korea: Kyung Eun Choi, Eun Yoon Cho, Chan Kum Park, Won Keun Lee, Young Hyeh Ko; J Korean Cancer Assoc. 1998;30(2):338-349.

Abstract PDF: PURPOSE
Epstein-Barr virus(EBV) exists in the human population in two genetic forms, usually referred to as type 1 and type 2 which have been defined on the basis of sequence divergence in the EBNA-2 and EBNA-3 family genes. In this study, we were intended to investigate whether the subtypes of EBV in malignant lymphoma in Korea were associated with specific disease entities and geographical distribution.
MATERIALS AND METHODS
Biopsy samples obtained from 18 Korean patients with malignant lymphoma including Hodgkin's disease(3 cases), B cell lymphoma(1 case), and NK/T cell lymphoma(14 cases) were analyzed to determine the subtype of EBV infected therein. DNA was extracted from formalin-fixed, paraffin-embeded tissues by ordinary method and specific viral sequences were sought using the polymerase chain reaction(PCR) and Southern blot hybridization assay. Oligonucleotide primers used for examination of EBV strain type were derived from the EBNA-3B and EBNA-3C coding regions. As a control, four cases of reactive hyperplasia were analyzed.
RESULTS
The two of four reactive hyperplasia cases were associated with type 1 and the rest of two cases with both types. Among the 18 cases with malignant lymphoma, thirteen cases(72%) had type 1, one(6%) had type 2, and four(22%) had dual infections with both types. In case of NK/T cell lymphoma(14 cases) occupying 78% of 18 biopsy samples, 86%(12 cases) were associated with type 1, 7%(1 case) with type 2, and 7%(1 case) with both types. In case of Hodgkin's disease, all of three cases had both types. B cell lymphoma taking only one case of twenty two cases was determined as type 1.
CONCLUSION
These observations indicated that type 1 EBV was predominant in Korean patients with malignant lymphoma, especially NK/T cell lymphoma and showed high frequency of dual viral infections(22%) in Hodgkin's disease as well as in reactive hyperplasia.

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Avascular Necrosis of Bone Complicating Treatment of Malignant Lymphoma: Report of 6 cases: Hyung Chan Suh, Jee Sook Hahn, Bum Seok Kim, Seok Lee, So Young Chong, Yoo Hong Min, Yun Woong Ko; J Korean Cancer Assoc. 1997;29(2):344-351.

Abstract PDF: BACKGROUND
Several reports have documented the association of avascular necrosis (AVN) of bone and the treatment of malignant lymphoma with steroid-containing chemotherapy. It is important to recognize these conditions, as they can be mistaken for those of lymphomatous involvement.Cases: This report describes the experience at the Severance hospital over a 10-year period with 6 patients in whom AVN developed during or following treatment of malignant lymphoma. Four patients of non-Hodgkin's lymphoma and two of Hodgkin's disease were treated with steroid-containing chemotherapy. The predominant symptom is pain on motion or weight bearing. Symptoms leading to diagnosis of AVN developed between 5 and 27 months after starting prednisolone (mean 17.8 months), and the mean cumulative dose of prednisolone to the onset of AVN was 4,447 mg (range, 1,800~9,490 mg). All but one were involved in both hip joint. Diagnosis was based on the radiologic appearance, and in the majority radiographic changes consistent with AVN were present at the time of presentation of symptoms. Four patients received total hip replacement and two had conservative care.
CONCLUSION
Patients with malignant lymphoma who developed pain on joint during or after the use of steroid-containing chemothearpy should be carefully investigated with MRI and radionuclear bone scan for early diagnosis and proper management.

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MACOP - B Chemthrapy for the Treatment of Malignant Lymphoma: Kyung Shik Lee, Hoon Kyo Kim, Young Seon Hong, Han Lim Moon, Je Ho Han, Chi Hong Kim; J Korean Cancer Assoc. 1990;22(1):112-116.

Abstract PDF: Between September 1987 and April 198S, 18 patients with advanced aggressive non-Hodgkin's lymphoma completed treatment with MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Among them, 14 patients were evaluable for the response and toxicity. Twelve patients (86%) achieved a complete response and 2 patients (14%,) had a partial response. The most frequent toxicity was leukopenia. Thus, MACOP-B is an effective and safe treatment for advanced aggressive lymphoma.

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Role of Chemofherapy in Unresectable Stage Biliary Tract Cancer: Hyun Cheol Chung, Eun Hee Koh, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(1):116-125.

Abstract PDF: Twenty evaluable patients with disseminated unresectable biliary tract cancer received chemotherapy after biliary tract drainage procedures. Two cambination chemotherapy protocols were applied; FAM (5-fluorouracil 1000 mg/m 24-hour infusion, day 1-3, adriamycin 40 mg/m i.v. day 1, mitomycin 10 mg/m i.v. day 1) in 13 patients, and MDF (5-fluorouracil 1000 mg/m' 24-hour infusion day 1-3, mitomycin 10 mg/m(2) i.v, day 1, cisplatin 80 mg/m i.v. day 4) in 7 patients. Course were repeated every three weeks. Seven patients(35%) achieved partial response. The median survival was 13.5 months in responders and 8.0 months in non-responders. No difference of drug response rate was observed between two chemotherapy protocols. Comparing the survival of biliary drainage plus chemotherapy group with that of billary drainage alone group, there was a trend of survival benefit in chemotherapy group with a median follow-up duration of 10 months. Gallbladder cancer and distal bile duct cancer showed favorable response rate and median survivals with chemotherapy and bile drainage than bile drainage alone. Most serious drug toxicities were myelosuppression and infection. But no chemotherapy related death was observed. Further randomized controlled trials to evaluate the effect of chemotherapy in advanced biliary tract cancer would be warrented.

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Combination Chemotherapy with 5-fluorouacil , ACNU and Mitomycin-C ( FUM ) for Carcinoma of the Pancreas and Gallbladder: Joong Jik Cha, Seok Kyun Kim, In Young Hyun, Weon Seon Hong, Jhin Oh Lee; J Korean Cancer Assoc. 1990;22(1):125-131.

Abstract PDF: Ten patients with pancreatic cancer and four with gailbladder cancer were treated with FUM: 5-fluorouracil (5-FU), ACNU and mitomycin-C (MMC): 5-FV 1,000 mg/m' i.v. on day 1 5, ACNU 60 mg/m(2) i.v. on day 1 and MMC 10 mg/m i.v. on day 5, everv four weeks. All patients had previously untreated and unresectable cancer due to direct invasion and/or distant metastasis. No complete response was observed. Three of 14 patients (21.4%) obtained partial response. Four patients (28.6%) showed no change and seven (50.0%) evidenced progressive disease. The median survival was 7.1 months for all patients, i.5 months for patients without metastasis and 3.8 months for patients with metastasis. Nine vf 14 patients (64.3%) have survived more than six months and four (28.6%) are still alive. Response rate were analyzed with regard to the age, sex, distant metastasis, serum carcinoem- bryonic antigen (CEA) level and jaundice. Patients with more than 50 years old, no metastasis, high CEA (>10 ng/ml) and low bilirubin (<2.0 mg/ml) showed higher response rate compared with those with less than 50 years old, metastasis, low CEA (<10 ng/ml) and high bilirubin (>=2.0 mg/ml), however, there was no statistical significance between these factors and response rate. The toxicity was mild to moderate. Patients were generally well tolerated, although all patients experienced nausea, vomiting and alopecia. Three patients had moderate degree of stomatitis and four showed severe myelosuppression for more than four weeks, however, myelosuppression was recovered by five or six weeks after treatment in all casea We think that these results provide a rationale for the conduction of the initiation of a large prospective randomized controlled trials with FVM therapy for the carcinorna of pancreas and gallbladder.

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The Treatment Results of Combination of Radiotherapy and chemotherapy in Limited Stage Small Cell Lyug Cancer: Chang Ok Suh, Jun Kyu Loh, Kyung Ran Park, Chang Ok Suh, Gwi Eon Kim, Jae Kyung Roh, Seong Kyu Kim, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(1):131-144.

Abstract PDF: A total of 72 patients with limited stage small cell lung cancer treated with combination of chemotherapy and radiotherapy at Department of Radiation Oncology, Yonsei University College of Meidcine between Jan. 1975 and Dec. 1986 were retrospectively analysed. 1) Age distribution of patients was between forty and seventy-one with median age fifty-five and male to female ratio was 5:l. 2) Complete response rate by treatment modality was as follows; CV+RT was 33.3%; CAV+RT, 43.59o, MOCA+RT. 28.6% and CAV+VP+RT was 62.5%. CAV+VP+RT group showed best result and this was statistically significant to MOCA+RT group (p=0.02) but insignificant to CV+ RT or CAV+RT grouP (P>0.1). 3) Median survival and 5 year actuarial survival rate by treatment modality were as follows; CVt RT was 15 3 months and 16.2%. CAV+RT, 14months and 16.396; MOCA+RT, 7month and 09; and CAV+ VP+ RT was 24 month and 30.7% respectively. CAV+VP+ RT groulp shawed the best results and these were statistically significant to MOCA+RT group(p<0.05) but insignificant to CV+RT or CAV+RT group (p>0,05). 4l Patterns of failure in complete response group were as follows; local failure was 24%, distant failure, 52% and local and distant failure was 24%. 5) Local control rate by radiation dosage in complete response group was as follows; when total dose of 4500-4900 cGv was given, local control rate was 50%; 5000 cGy, 43% however when total dose was given between 5100-7000 cGy, local control rate was significantly improved to 100%. 6) The incidences of brain metastsis in PCI (prophylactic cranial irradiation) group and control group were 20% and 32% respectively, although this was statistically insignificant (p=0.32). 7) Statistically significant factors affecting prognosis were performance status, TNM stage, initial status of presentation of superior vena cava syndrome and pleural effusion, location of tumor, response status to treatment and whether or not maintenance chemotherapy is added.

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Treatment of Advance Inoperable Stomach Cancer with Cisplatin Adriamycin and 5-FU ( FAC: Duck Kyung Gong, Sang Wook Lee, Byung Hoon Han, Seung Yeon Suh, Man Ha Huh, Byung Chae Park; J Korean Cancer Assoc. 1990;22(1):144-151.

Abstract PDF: Twenty-four evaluable patients with advanced inoperable stomach cancer were treated with a combination of cisplatin (40 mg/m, IV, day 1), Adriamycin (30 mg/m, IV, day 2) and 5-FU (500 mg/ m, IV, day 3-5) every three weeks. The tumor responses and survival of the treated patients were compared to the untreated control patients (15 cases) who had similar tumor burden and performance status. There were four objective partial resPonses, giving a response rate of 16.7%. Eleven patients (45.8%) achieved disease stabilization and 9 cases (37.596) had tumor progression. No complete response was observed. FAC produced signficantly (P<0.0i) superior overall survival comPared to cvntrol. One-year survival rate for FAC regirnen was 53% compared to 15% for the control and median survival times ware 12.5 months versus 6 months, respectively. Toxicity was moderated and consisted of nausea, vomiting and hair loss. In conclusion, FAC regimen appears to have not so satisfactory effect in tumor responses in patients with advanced stomach cancer, but it is helpful for prolongation of survival times as compared to the untreated control patients.

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2 Cases of Primary Uterine Lymphoma: Seok Nam Yoon, Young Yiul Lee, In Soon Kim, Kyung Tai Kim, Byung Hee Ko, Young Hyeh Ko; J Korean Cancer Assoc. 1994;26(6):1005-1013.

Abstract PDF: Primary Uterine lymphoma is a rare presentation of extranoal lymphoma: therefore, informations regarding histologic type, immunophenotype of tumor cell and etiologic factors are limited. Usually uterine cervix was predominant 1ocation in primary uterine lyphoma and most patients reported abnormal vaginal bleeding as a initial presentation in uterine lymphoma. Histologically, approximately 70% of all uterine lymphoma were diffuse large cell type by Working Formulation. Recently We experienced two cases of uterine lymphoma, one from uterine cervix, the other from uterine corpus. A uterine cervix lymphoma was diagnosed by colposcopic punch biopsy. A uterine corpus lymphoma was suggested by MRI findings; diffuse uterine enlargement without contour alteration of endometrium, and confirmed by deep cervical punch biopsy. Two cases were found to have diffuse large cell lymphoma and immunologically one was Bll lineage, the other T-cell lineage. Two case were treated with chemotherapy only. We report these cases with literature review.

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High - dose Chemotherapy with Hematopoietic Stem Cell Support for Malignant Lymphoma: Young Suk Park, Jung Ae Lee, Woo Sung Min, Seonyang Park, Jing Shin Lee, Hugh Chul Kim, Hoon Kook, Jong Ho Won, Dae Sik Hong, Hee Sook Park; J Korean Cancer Assoc. 1996;28(2):316-326.

Abstract PDF: Patients with intermediate or high-grade non-Hodgkin's lymphoma(NHL) have been reported a 40% to 70% cure rate when treated with conventional chemotherapy or radiotherapy. However, most of the patients who do not attain complete remission(CR) or who relapae after chemotherapy are incurable using conventional salvage therapies and these individuals have potential for cure with high-dose therapy with reinfusion of stem cells derived from bone marrow or peripheral blood. Between February 1993 and September 1995, 26 patients with aggressive, relapsed and/or refractory malignant lymphoma were treated with high-dose chemotherapy with either autologous peripheral blood stem cell(25 patients) or bone marrow(l patient) support in 7 university hospitals in Korea. The median age was 39 years(range, l7 to 69) and male to female ratio was 4.2: 1. The common histologic types were diffuse large cell(42%), immunoblastic type(15%) of non-Hodgkin's lymphoma. The rate of complete remission was 61%(14/23) and overall remission rate was 78%(18/ 23) for the patients with measurable disease. Three patients were treated as the consolidation therapy in the status of complete remission. The median duration of remission was not reached right now. The median survival time was 7.8 months for all patients(the median follow up time; 9 months). The median time to recovery to a neutrophil count more than 0.5 x 10(9)/L was 13 days(range, 8 to 43), and to 1 x 10(9)/L was 22 days(range, 8 to 53). The median time to recovery of platelet count more than 50 x l0(9)/L and 100 x 10(9)/L were 20 days(range, 8 to 45) and 21 days(ranae, ll to 60). Non-hematologic side effects were fever, nausea and vomiting, and liver toxicity. Two toxic deaths occurred due to cardiovascular disease, mainly congestive heart failure. Based on high complete remission rate and tolerable toxicity, high-dose chemotherapy with hematopietic stem cell support appears to be a promising treatment modality for the patients with aggressive, relapsed and/or refractory malignant lymphoma.

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