Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

BACKGROUND: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). METHODS: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. RESULTS: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. CONCLUSIONS: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Angiocentric lymphoma of the head and neck: patterns of systemic failure after radiation treatment.

PURPOSE: To investigate the patterns of systemic failure and the clinical outcome in patients with angiocentric lymphoma of the head and neck who were treated with radiation alone, and to discuss the optimal mode of treatment for these patients. PATIENTS AND METHODS: We reviewed the records of 92 patients with stage I or II angiocentric lymphoma who were treated at Yonsei Cancer Center between 1976 and 1994. All patients were treated with involved-field irradiation. Radiation doses ranged from 40 to 60 Gy (median dose, 50.4 Gy). Treatment response, patterns of treatment failure including systemic failure, and clinical outcome after radiation treatment were analyzed. RESULTS: The most frequently involved site was the nasal cavity, either alone or in conjunction with other sites. In 16 patients (17.4%), angiocentric lymphoma was accompanied by cervical lymphadenopathy. Disease was classified as stage I in 62 patients (67.4%) and stage II in 30 patients (32.6%). After completion of radiation treatment, 61 patients (66.3%) achieved a complete response and 16 (17.4%) a partial response. Half of the patients (50.0%) ultimately experienced local recurrence with or without other components of failure, whereas regional failure was relatively uncommon (10.9%). Systemic failure occurred in 25.0% of patients during follow-up. Six patients had histologic findings identical to those at the time of the original disease (group I), whereas four patients exhibited morphologic features of frank lymphomas (group II). The majority of patients with systemic relapse had the predilection sites for widespread extranodal involvement, such as the skin, brain, lung, gastrointestinal tract, or testes. In addition, seven patients died from various medical illnesses or immunologic disorders, including hemophagocytic syndrome and second primary cancers (group III). After a median follow-up of 56 months, the overall survival and disease-free survival rates for all patients were 40.1% and 37.8%, respectively. All patients except one with systemic failure died within 1 year. CONCLUSION: Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.

Adaptive response to ionizing radiation induced by low doses of gamma rays in human cell lines.

PURPOSE: The aim of this study was to investigate whether the adaptive response could be induced in human lymphoblastoid cell lines and human tumor cell lines. The time necessary for the expression of the adaptive response was also investigated. MATERIALS AND METHODS: Three lymphoblastoid cell lines from ataxia telangiectasia (AT) homozygote (GM 1526), AT heterozygote (GM 3382), and normal individual (3402p) and two hepatoma cell lines, Hep G2 and Hep 3B, were used in this study. Experiments were carried out by delivering 0.01 Gy followed by 0.5 Gy of gamma radiation to the exponentially growing cells. The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 to 72 h. In some experiments, 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, was added immediately after the 0.5 Gy exposure. The cultures were fixed 30 min (for the G2 chromatid) and 6 h (for the S chromatid) after the 0.5 Gy exposure. Metaphase chromosome assay was carried out to score chromatid breaks as an end point. RESULTS: A prior exposure to 0.01 Gy of gamma rays significantly reduced the number of chromatid breaks induced by subsequent higher doses (0.5 Gy) in all the tested cell lines. The magnitude of the adaptive response was similar among the cell lines despite their different radiosensitivities. In the G2 chromatids, the adaptive response was observed both at short-time intervals, as early as 1 h, and at long-time intervals. In the S chromatids, however, the adaptive response was shown only at long-time intervals. When 3-aminobenzamide was added after the 0.5 Gy, the adaptive responses were abolished in all the experimental groups. CONCLUSION: The adaptive response was observed in human lymphoblastoid cell lines and hepatoma cell lines. The magnitude of the adaptive response did not seem to be related to the radiosensitivity of the cells. The elimination of the adaptive response with 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanisms.

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer.

PURPOSE: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. METHODS AND MATERIALS: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. RESULTS: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). CONCLUSION: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer.

Early alteration in TGF-beta mRNA expression in irradiated rat liver.

PURPOSE: Radiation of the liver results in hepatic fibrosis as a late complication. TGF-beta has been implicated in the pathogenesis of fibrosis. The purpose of this study was to determine if there is early alteration in TGF-beta expression before hepatic fibrosis is evident. METHODS AND MATERIALS: Male Sprague-Dawley rats weighing 150-175 g were used. A partial volume of liver as large as a 2 cm x 1 cm rectangle was given a single dose of 25 Gy gamma radiation. Animals were sequentially sacrificed from day 0 to day 28. Appearance of hepatic fibrosis was tested by trichrome stain. Levels of mRNA expression of TGF-beta1 and TGF-beta3 were measured by Northern blot hybridization. Change in the level of mRNA expression was analyzed by densitometry. The expression of TGF-betas was also analyzed in tissue with immunohistochemical staining. RESULTS: In trichrome-stained liver tissues obtained through 28 days after irradiation, there was no evidence of hepatic fibrosis. The expression of mRNAs of TGF-beta1 and TGF-beta3 showed different features; The level of TGF-beta1 mRNA showed a gradual increase to the peak level of 3.6-fold at day 28, the last analyzed time. In contrast, TGF-beta3 mRNA showed an early peak of 4.8-fold at day 7 followed by a decrease to the lowest level of 1.6-fold at the last analyzed time. The expression of TGF-betas was also analyzed in tissue with immunohistochemical staining. At day 28 after radiation, increased positive staining for TGF-beta1 was observed around the central vein. Positive staining appeared mainly in nonhepatocytic cells. For TGF-beta3, the same pattern of positive staining was observed at day 7. CONCLUSION: The results of this study suggest that the alteration in mRNA expression of TGF-beta1 and TGF-beta3 occurs very early after radiation. The contrasting difference in the mRNA expression pattern of TGF-beta1 and TGF-beta3 suggests that interaction of the TGF-betas may be involved in fibrogenesis of irradiated liver, with TGF-beta1 as a positive regulator and TGF-beta3 as a negative regulator.

Sensory and motor dysfunction assessed by anorectal manometry in uterine cervical carcinoma patients with radiation-induced late rectal complication.

PURPOSE: To investigate the effects of radiation on anorectal function in patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Anorectal manometry was carried out on 24 patients (complication group) with late radiation proctitis. All of the manometric data from these patients were compared with those from 24 age-matched female volunteers (control group), in whom radiation treatment had not yet been performed. RESULTS: Regardless of the severity of proctitis symptoms, 25% of patients demonstrated all their manometric data within the normal range, but 75% of patients exhibited one or more abnormal manometric parameters for sensory or motor functions. Six patients (25%) had an isolated sensory dysfunction, eight patients (33.3%) had an isolated motor dysfunction, and four patients (16.7%) had combined disturbances of both sensory and motor functions. The maximum tolerable volume, the minimal threshold volume, and the urgent volume in the complication group were significantly reduced compared with those in the control group. The mean squeeze pressure in the complication group was significantly reduced, whereas the mean resting pressure and anal sphincter length were unchanged. CONCLUSIONS: Physiologic changes of the anorectum in patients with late radiation proctitis seem to be caused by a variety of sensory and/or motor dysfunctions in which many different mechanisms are working together. The reduced rectal reservoir capacity and impaired sensory functions were crucial factors for functional disorder in such patients. In addition, radiation damage to the external anal sphincter muscle was considered to be an important cause of motor dysfunction.

Assessment of biomarkers in paired primary and recurrent colorectal adenocarcinomas.

PURPOSE: Recurrent colorectal cancers respond poorly to anticancer treatment including radiotherapy. To better understand the biological characteristics of the recurrent colorectal tumor, we investigated various biomarkers regulating cell proliferation and cell loss in paired primary and recurrent colorectal tumor specimens within each individual. METHODS AND MATERIALS: From a total of 11 colorectal adenocarcinoma patients, 22 specimens of paired primary and recurrent tumors were obtained for analysis. Apoptosis was evaluated by TUNEL labeling of apoptotic DNA fragmentation. Other biomarkers including proliferating cell nuclear antigen (PCNA), p53, WAF1, p34cdc2, and cyclins B1 and D1 were analyzed by immunohistochemical stains. RESULTS: PCNA index (PCNAI) showed an increase in 6 and a decrease in 5 recurrent tumors compared to primary tumors. Median PCNAI in primary and recurrent tumors were 33.5 and 48.3, respectively (p = 0.16). In contrast, the apoptotic index (AI) decreased in 9 of 11 recurrent tumors compared to primary tumors. Median AI decreased from 4.3 in primary tumors to 1.4 in recurrent tumors (p = 0.04). The p53 expression increased in more than half of recurrent tumors compared to primary tumors. Mean staining score increased from 0.7 in primary tumors to 1.2 in recurrent tumors (p = 0.059). WAF1 and cyclin B1 did not show significant change. In contrast, both cyclin D1 and p34cdc2 increased significantly in recurrent tumors. These two biomarkers showed increased expression in 8 (cyclin D1) and 7 (p34cdc2) recurrent tumors, respectively, compared to their primary counterparts. Mean staining scores of both biomarkers in recurrent tumors increased by more than twofold compared to those in primary tumors and these differences were statistically significant (cyclin D1, p = 0.007; p34cdc2, p = 0.008). CONCLUSION: This study showed significantly decreased apoptosis in recurrent colorectal tumors compared to their primary counterparts. The underlying regulatory mechanisms included increased expression of p53 and altered cell cycle regulators such as increased cyclin D1 and p34cdc2. With further study, it may be used for developing a new therapeutic strategy for the treatment of recurrent colorectal cancer.

Local radiotherapy for unresectable hepatocellular carcinoma patients who failed with transcatheter arterial chemoembolization.

PURPOSE: The purpose of this study was to investigate the efficacy of local radiotherapy (RT) as a salvage treatment for unresectable hepatocellular carcinoma (HCC) patients who failed with transcatheter arterial chemoembolization (TACE). METHODS AND MATERIALS: Patients with unresectable HCC who had been treated with and eventually failed with TACE were eligible. The judgment of TACE failure was based on incomplete tumor filling of lipiodol-adriamycin mixture on either angiography or computed tomography (CT) scan. From January 1993 to December 1997, 27 patients were entered into this study. They had UICC Stage III (17) or IVA (10) disease, with a mean tumor size of 7.2 +/- 2.9 cm. Local RT was done, with a mean tumor dose of 51.8 +/- 7.9 Gy, in daily 1.8-Gy fractions using a 10- or 6-MV linear accelerator. Survival was calculated from both the diagnosis and the start of RT using the Kaplan-Meier method. RESULTS: An objective response was observed in 16 of 24 patients (66.7%) including 1 CR. Intrahepatic metastasis was noted outside the RT field in 10 patients (37.0%). Extrahepatic distant metastasis occurred in 4 patients. Survival rates at 1, 2, and 3 years were 85. 2%, 58.1%, and 33.2%, respectively, from the diagnosis and 55.9%, 35. 7%, and 21.4%, respectively, from the start of RT. The median survivals were 26 months from the diagnosis and 14 months from the start of RT. Acute toxicity involved alteration in liver function test (13 patients) and thrombocytopenia (2 patients). Subacute and chronic toxicity involved gastroduodenal ulcer (3 patients) and duodenitis (2 patients). There was no treatment-related death. CONCLUSION: In unresectable HCC patients who failed with TACE, local RT induced a substantial tumor response of 66.7%, with a 3-year survival rate of 21.4% and a median survival time of 14 months. Toxicity was significant but manageable. Although we do not know if there is survival benefit through this treatment, local RT in these patients seems to be valuable as a salvage for TACE-failed HCC.

The role of radiation treatment in management of extrahepatic biliary tract metastasis from gastric carcinoma.

PURPOSE: To determine the proper role of radiation treatment in the management of patients with extrahepatic biliary tract metastasis due to recurrent gastric cancer. METHODS AND MATERIALS: Twenty patients with malignant biliary obstruction due to recurrent gastric carcinoma after gastrectomy were treated with palliative intent at the Yonsei University College of Medicine from 1986 to 1990. Treatment consisted of external drainage alone in 11 patients (Group I) and external drainage followed by radiation treatment in nine patients (Group II). Five of nine patients in Group II underwent external irradiation in combination with intraluminal brachytherapy using high dose rate Iridium-192 (Ir-192) sources within the expandable intrabiliary prosthesis, a Gianturco stent, inserted transhepatically at the site of obstruction. RESULTS: An excellent local response was observed in five of nine patients in Group II, in whom biliary patency was restored following treatment so that the external drainage catheter could be removed. Prolongation of median survival was observed in Group II (9 months) as compared to Group I (2 months). There were no serious treatment-related complications with this approach. CONCLUSION: This treatment approach with external radiotherapy +/- intraluminal brachytherapy could achieve effective palliation and improve the quality of life in selected patients with extrahepatic biliary metastasis from gastric carcinoma.

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.

Phase II trial for combined external radiotherapy and hyperthermia for unresectable hepatoma.

Hepatocellular carcinoma is a major malignant disease in parts of Africa and Asia, including Korea. Surgical resection, which represents the best hope for cure, is limited by the extent of the disease and the high incidence of concurrent liver cirrhosis in Korea. We designed a phase II trial of combined external radiotherapy and hyperthermia for hepatocellular carcinoma that was unresectable due to either locally advanced lesions or associated liver cirrhosis so as to evaluate the efficacy and the safety of this combination regimen. This trial was performed at Yonsei Cancer Center between April 1988 and July 1988. External radiotherapy was delivered to a total dose of 3060 cGy/3.5 weeks. Hyperthermia was applied twice a week for a total of six treatment sessions using an 8-MHz radio-frequency capacitive-type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases, hyperthermia was carried out within 30 min of the radiotherapy for a period of 30-60 min. The temperature in the tumor was measured by inserting a thermocouple into the tumor mass under ultrasonographic guidance in patients who did not have a bleeding tendency. The tumor response was assessed by CT scan after completion of the designed treatment. No complete response was obtained. However, a symptomatic improvement in abdominal pain was observed in 78.6% of cases and a partial response was achieved in 40% of the patients. The most important factor affecting the tumor response was the type of tumor (single massive, 71.4%; diffuse infiltrative, 20%; multinodular, 0; P < 0.005). The 1-year survival values determined for all patients and for the partial responders were 34% and 50%, respectively. The overall median duration of survival was 6.5 months. The median duration of survival for the partial responders was longer than that for the nonresponders (11 vs 5 months; P < 0.05). A mild degree of heat sensation, fever, first-degree burns of the skin, and nausea were observed as treatment-related adverse reactions. In conclusion, although this study is being continued, the results obtained thus for indicate that combined radiotherapy and hyperthermia seem to be effective in providing local tumor control and pain palliation in unresectable hepatocellular carcinoma while producing an acceptable level of toxicity.

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study.

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.

Prevention of heterotopic bone formation after total hip arthroplasty using 600 rad in single dose in high risk patient.

Nineteen patients received single-dose exposure to 600 rad delivered within 48 hours of total hip arthroplasty (THA) with shielding of the prosthesis region for the prevention of heterotopic ossification. The patients were considered at high risk for developing heterotopic ossification (HO) because of hypertropic osteoarthritis, post-traumatic osteoarthritis or the presence of previously-formed ectopic bone. The average follow-up period was 42 months (range, 37 months-48 months). At a follow-up study, all hips except one were classified as Brooker class 0. The single exception was classified as class I. All patients were asymptomatic at the last follow-up study and no component demonstrated subsidence or radiolucent line indicative of loosening. The authors concluded that 600 rad, single-fraction radiation therapy is cost effective, convenient and safe for the prevention of heterotopic ossification after total hip arthroplasty.

Primary lymphoma of the eye.

Lymphomas in the eye tend to be localized and to have a better prognosis. We reviewed the clinical presentation, treatment outcome and complications of primary lymphomas of the eye at a single institute focusing on the clinical significance of adequate staging and the prognostic value of pathological subtypes. Twenty-four patients with lymphoproliferative lesion of the eye were treated and followed up. The orbit was the most commonly involved site. Twenty-one patients had unilateral diseases and three patients had bilateral. Histological findings revealed 22 malignant lymphomas, one inflammatory pseudotumor and one atypical lymphoid hyperplasia. Using the NCI Working Formulation, most of the malignant lymphomas were primarily low grade: diffuse small lymphocytic, 15; diffuse small cleaved three; diffuse large cell, three; and diffuse mixed, one. The stages of lymphoma were IAE in 21 patients, IBE in one patient, and IIAE in two patients. Twenty-five of the 27 treated eyes remained disease-free during the median follow-up period of 16 months. Nineteen patients received radiotherapy, five patients received chemo-radiotherapy and one patient received only surgical excision. Two patients relapsed outside the treated field. None of the patients complained of severe dry eye syndrome or cataract formation. In conclusion, after complete staging work-up, locally-confined low grade orbital lymphomas can be up to 90% controlled with radiotherapy alone. By contrast, combined treatment is advised in patients with intermediate and high grade lesions.

The role of radiotherapy in the treatment of aggressive fibromatosis.

Aggressive fibromatosis is a rare benign soft tissue tumor that is difficult to cure because of its infiltrative nature and high tendency to recur locally. The authors retrospectively analyzed 20 patients with histologically-confirmed fibromatosis. All patients underwent surgery with a wide or marginal margin. Five (25%) cases with histologically-negative margins had recurred. External beam radiotherapy was administered to patients whose margins were positive or who had local recurrence. However, out of concern for safety, radiotherapy was not given to two babies and a reproductive-aged woman. The average dose was 5,020 cGy. During the follow-up (mean 32.6 months), all the patients undergoing radiotherapy showed no evidence of local recurrence. A wide local excision has traditionally been the treatment of choice. However, postoperative radiotherapy could be an effective measure for preventing local recurrence in patients with a histologically-positive surgical margin and recurrence independent of any signs of relapse.

Primary lymphoma of the thyroid.

Primary lymphoma presenting in the thyroid gland is uncommon. A review of the Yonsei University Medical Center experience between 1982 and 1994 was performed retrospectively to assess the treatment outcome and prognostic factors. There were four females and one male, and the median age was 65 years. All 5 cases presented with a neck mass. Two of them had co-existing biopsy-proved Hashimoto's thyroiditis and three cases were each in a hypothyroid state. All cases with non-Hodgkin's disease were of intermediate grade. One case was in stage IE and four were in stage IIE. Three cases were treated with surgery alone and two cases with bulky inoperable stage IIB were treated with chemo-radiotherapy. Chemotherapy induced a complete response in one and a partial response in the other with minimal transient toxicity. As the questions regarding justification for extensive surgical intervention increase, combined chemo-radiotherapy can be suggested as an initial treatment even in stage I, and stage II thyroid lymphoma based on prognostic factor evaluation.

Combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma.

Eighty-four patients with unresectable primary hepatocellular carcinoma due either to locally advanced lesion or to association with liver cirrhosis were treated with combined radiotherapy and hyperthermia from April 1988 to January 1991. Purpose of this study was to assess thermometry, response rate, toxicity, and survival in those patients. External radiotherapy was given with a total of 30.6 Gy/3.5 wks. Hyperthermia was given twice a week with a total of 6 treatment sessions using an 8 MHz radiofrequency capacitive type heating machine. Each hyperthermia session was started within 30 min following radiotherapy and continued for 30-60 min. Thermal data were analysed with maximum, minimum, and average temperatures of the tumors. Thermal mapping was also done. In thermometry results, maximum, minimum, and average temperatures of the tumors were 41.9 +/- 1.3 degrees C, 39.9 +/- 1.0 degrees C, and 40.8 +/- 0.9 degrees C, respectively. The fraction over 40 degrees C was 73 +/- 32% with a wide variation from 15% to 100%. Among 67 assessable patients, 27 patients showed tumor regression of more than 50% of the original tumor volume (40.3% response rate). Symptomatic improvement was observed in 78.6% of the patients. Acute toxicities during the treatment were mostly acceptable local pain (51.2%) and local fat necrosis (13.1%). The actuarial 1-year, 2-year, and 3-year survival rates were 44.8%, 19.7%, and 15.6%, respectively. Median survival was 6 months. In view of acceptable toxicities and the current rate of survival, further evaluation of combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma is warranted.

Partial mastectomy with axillary lymph node dissection and radiotherapy as a new treatment modality of breast cancer (I).

This is the first preliminary report among two consecutive papers. Partial mastectomy(PM), axillary lymph node dissection(AD) and radiotherapy (RT) were performed on seventeen operable breast cancer patients who had been admitted from April 1991 to March 1992 to the department of surgery, Yongdong Severance Hospital for improved cosmetic appearance and better survival rate. Of seventeen patients, 47% were T1 lesion and 76% were stage I and II. Extensive intraductal component(EIC) within or around the tumor was also analyzed. Twenty nine per cent of the patients were EIC positive. The mean number of axillary lymph nodes was 21.5 after PM with AD and 20.5 after mastectomy. For radiotherapy, 4,500 rad was delivered to the breast parenchyma and 1,600 rad of boost to the primary tumor site using the electron beam method after surgery. All patients have since been living well without any local recurrence and were satisfied with breast preservation for the one-year follow-up period. We concluded that the PM, AD and RT can be another surgical treatment modality of breast cancer. A longer follow-up data will be followed on the second paper.

Hyperfractionated re-irradiation using a 3-dimensional conformal technique for locally recurrent carcinoma of the nasopharynx; preliminary results.

To evaluate the efficacy of hyperfractionated re-irradiation using a three-dimensional conformal radiotherapy (3-D CRT) technique in patients with locally recurrent carcinoma of the nasopharynx. Four patients with locally recurrent nasopharyngeal cancer were retreated with a hyperfractionated schedule using a 3-D CRT technique. Re-irradiation was delivered in 1.1-1.2 Gy fractions twice per day (BID), with interfraction intervals of more than 6 hours. The total dose ranged from 59.4 to 69.2 Gy. A 3-D CRT technique with 5- or 6-field coplanar and/or non-coplanar beams were employed during the entire treatment procedure. All four patients achieved complete remission of locally recurrent lesions, with marked improvement of subjective symptoms, immediately after re-irradiation. All are alive and well without evidence of disease after limited follow-up periods, which range from 7 to 20 months. So far, there have been no radiation-induced neurologic complications. Four patients with locally recurrent carcinoma of the nasopharynx were successfully treated by hyperfractionated re-irradiation using a 3-D CRT technique. A relatively high re-irradiation dose of more than 60 Gy may be safely delivered with no serious acute or late radiation-induced complications in patients with local recurrences and who were initially treated with doses greater than 70 Gy.

Non-Hodgkin's lymphoma & primary biliary cirrhosis with Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by a lymphocytic infiltration of the salivary and lacrimal glands leading to a progressive destruction of these glands due to the production of autoantibodies. This disorder is either isolated (primary SS) or associated with other systemic diseases (secondary SS). The occurrence of B-cell non-Hodgkin's lymphoma (NHL) represents the major complication in the evolution of SS patients. The risk of developing NHL, which is equivalent for both primary and secondary SS, was estimated to be 44 times greater than that observed in a comparable normal population. NHLs in SS patients occur preferentially in the salivary glands and in other mucosa-associated lymphoid tissues (MALT). However, it can also occur in the lymph nodes or bone marrow. We documented a case of low-grade B-cell lymphoma of MALT in the right eyelid and primary biliary cirrhosis (PBC) of a patient with SS. To the best of our knowledge, this is the first case reported in Korea.