BFM-90、CHOP和 CHOP/HD-MTX方案治疗儿童青少年 B细胞非霍奇金淋巴瘤的生存率比较

背景与目的：儿童青少年B细胞非霍奇金淋巴瘤(B cell non-Hodgkin’s lymphoma,B-NHL)恶性程度高、进展快、早期患者对常规CHOP方案化疗可获得较好疗效,但晚期患者疗效差。对不同分期的患者应如何治疗值得进一步探索。本文回顾性分析和比较CHOP、CHOP HD-MTX和德国BFM-90方案治疗儿童青少年B-NHL的疗效、不良反应和生存率。方法：CHOP方案组30例3～17岁初治的B-NHL患者,Ⅰ／Ⅱ期13例,Ⅲ／Ⅳ期(St Jude分期)17例,均接受2～8疗程常规CHOP方案化疗,每3周重复。CHOP HD-MTX组18例3～14岁初治的B-NHL患者,Ⅰ／Ⅱ期6例,Ⅲ／Ⅳ期(st Jude分期)12例,均接受2～8疗程CHOP HD-MTX方案化疗和鞘注,每4周重复。BFM-90方案组25例1．5～15岁的初治的B-NHL患者,Ⅱ期7例,Ⅲ／Ⅳ期(St Jude分期)18例,均接受NHL-BFM-90方案化疗。Ⅰ／Ⅱ期患者接受A和B疗程交替化疗共4～6疗程;Ⅲ／Ⅳ期患者接受AA和BB疗程交替化疗共6疗程,每疗程间隔18～21天。结果：CHOP组21例(70％)完全缓解(complete response,CR),4例(13％)部分缓解(partial response,PR);有20％的疗程发生Ⅲ／Ⅳ级血液毒性。CHOP HD-MTX组15例(83％)CR,3例(16％)PR;有52％疗程发生Ⅲ／Ⅳ级血液毒性。BFM-90方案组24例(96％)CR,1例(4％)PR;Ⅲ／Ⅳ级血液毒性：A疗程57％,B疗程60％,AA疗程91％,BB疗程76％;AA疗程的血液毒性明显高于其他疗程。Ⅱ／Ⅲ级粘膜炎主要发生在AA和BB疗程,占35％。三组均按Kaplan-Meier方法进行生存率统计。CHOP组2年总生存率52．79％,Ⅰ／Ⅱ期患者72．73％,Ⅲ／Ⅳ期37．82％。CHOP HD-MTX组2年总生存率55．56％,Ⅰ／Ⅱ期患者83．33％,Ⅲ／Ⅳ期41．67％。CHOP组患者生存率与CHOP HD-MTX组比较无显著性差异(P=0．78)。BFM-90方案组2年无事件生存率84．01％,Ⅰ／Ⅱ期患者100．00％,Ⅲ／Ⅳ期患者77．04％。BFM-90方案组生存率与CHOP组和CHOP HD-MTX组比较有显著性差异(P=0．013,0．034)。结论：BFM-90方案能明显提高儿童青少年B-NHL的生存率,特别是对晚期患者的疗效改善更明显。CHOP和CHOP HD-MTX对早期患者可获得较好的疗效,但对晚期患者疗效差。对晚期B-NHL应采用类似BFM-90方案的高强度化疗。     

Prognostic factors in non-Hodgkin's lymphoma

The results obtained with the various types of treatment in non-Hodgkin's lymphoma are reviewed and the data from the recent EORTC trials are summarized. In patients with Stage I follicular histology, regional radiotherapy (RT) alone gives excellent results. The long-term relapse-free survival (RFS) is high and relapsing patients can be rescued by aggressive combination chemotherapy; initial chemotherapy with CVP improves RFS but not total survival (TS). In patients with Stage I diffuse histology, the long-term survival is less satisfactory. CVP chemotherapy does not improve either RFS or TS; therefore if adjuvant chemotherapy is justified, it should be more aggressive than CVP. In patients with Stage II follicular type, regional radiotherapy alone gives good results. The addition of abdominal bath irradiation to regional RT increases RFS but not TS. After relapse, patients can be rescued by combination chemotherapy. In patients with Stage II diffuse histology, extended RT followed by CVP gives poor results and RT should be combined with more aggressive combination CT; the preliminary results of an integrated alternating regimen being excellent. In patients with Stage III and IV follicular type, the 8 year TS of patients treated with combination CT regimen (CHVP) followed by localized irradiation is approximately 55%, however the indications for the various types of treatment are still unclear. In patients with diffuse Stage III and IV, the results obtained with a combination CT regimen (CHVP) are still unsatisfactory, but are better in patients treated by a more aggressive CT regimen (CHVP-Bleo-VCR). Therefore aggressive CT associated with localized irradiation appears to be the best treatment. Further research should aim to identify the optimal combination CT regimen. In patients with high grade lymphomas who have relapsed the use of bone marrow autografts will be investigated. The present data show that besides histological type and age, the main prognostic factor is total tumor body burden as assessed by clinical stage, number of involved lymph node areas, and bulk of the disease. The study of the biological characteristics of the disease may provide more powerful prognostic indicators.     

Large noncleaved follicular center cell lymphoma. Clinical features in 53 patients

To clarify the clinical characteristics of large noncleaved lymphoma (LNC-FCC; intermediate grade, large cell, noncleaved, Working formulation), 53 patients were studied. Thirty-one were male and 22 female. Median age was 54 years. Initial symptoms included lymphadenopathy (40%), pain (34%), and B symptoms (21%). Stage I disease was present in 6, Stage II in 9, Stage III in 14, and Stage IV in 24 (72% Stage III or IV). Gastrointestinal (GI) tract involvement was present in 13. Central nervous system (CNS) disease was present at diagnosis in two patients, occurred during therapy in two, and was the sole site of relapse in two. Bone marrow involvement was found in 7 of 50 patients (14%). Complete remission was attained in 60% of all patients. Twenty-nine Stage III and IV patients received intensive multiagent chemotherapy; complete remission (CR) was attained in 69%. In contrast, zero of nine patients with Stage III or IV disease who did not receive an anthracycline-containing regimen, attained CR. Median survival for the entire group was 25 months. It was concluded that, in our patients with LNC-FCC, GI involvement was prominent (25%) and CNS disease was not uncommon (11%). Long-term disease-free survival may be achieved in patients with more advanced disease after the administration of anthracycline-containing combination chemotherapy.     

Radiation therapy for nasopharyngeal carcinoma. Retrospective review of 105 patients based on a survey of Kansai Cancer Therapist Group

One hundred five patients with nasopharyngeal carcinoma were treated with radiation therapy combined with or without chemotherapy at 16 of the participating institutes in Kansai Cancer Therapist Group, Japan, from January 1978 to December 1980. The study comprised 77 males and 28 females; their ages ranged from 15 to 80 years (mean, 53 years). Five-year survival rates according to stage were as follows: Stage I, 100%; Stage II, 67%; Stage III, 44%; and Stage IV, 34%. As far as Stage IV disease was concerned, the radiation therapy only group showed significantly poorer prognosis than the combined radiation and chemotherapy group (P less than 0.05). Concerning the N stage and treatment method, the radiation therapy only group showed a higher metastatic rate than the chemotherapy combined group (35% versus 14%, P less than 0.05).     

Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

PURPOSE: To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS: After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.     

Invasive carcinoma of the uterine cervix in women age 25 or less

The incidence of cervix cancer in young women appears to be increasing. However, the influence of young age on prognosis remains unknown. There is almost no information on the prognosis of very young women, age 25 years or less, with invasive cervical carcinoma. From April 1969 to June 1987, 40/2195 (1.8%) patients, age 25 years or less, with invasive carcinoma of the uterine cervix were diagnosed, staged, and treated at our institution. Median age was 24.7 years (range 20.7 to 25.9 years). Distribution by FIGO stage was: Stage IA 7 (18%), Stage IB 23 (58%), Stage II 4 (10%), Stage III 4 (10%), and Stage IVA 2 (4%). Thirty-four (85%) patients had squamous cell carcinoma and six (15%) had adenocarcinoma. Treatment consisted of radical hysterectomy for all Stage IA patients, radical hysterectomy with or without bilateral pelvic node dissection for the 12 early Stage IB patients, and radiation with or without surgery for the remaining 11 Stage IB patients and all Stage II-IVA patients. Median follow-up was 122 months (range 13.2-190.6 months). Five-year disease-free survival rates were: Stage IA 100%; Stage IB 54.8%; and Stage II-IVA 13.7%. Five-year disease-free survival for the Stage IB patients with squamous cell carcinoma age 25 years or less was 64.7%, compared with 83% for women of all ages with Stage IB squamous histology treated at our institution. Seven of 23 Stage IB patients suffered regional recurrence only, one a local recurrence only, one a distant recurrence only, and one a combined recurrence. Seventy-five percent of these patients presented with Stage I disease; however, one-third died from their disease. The major site of failure was in the pelvis only. This, coupled with the low risk of long-term serious complications, suggests that more aggressive pelvic therapy may result in improved disease-free survival.     

Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy

Purpose: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy.

Methods and Patients: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease.

Results: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69.4% (p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% (p = 0.0001).

Conclusion: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.     

Treatment of pediatric Hodgkin's disease with chemotherapy alone or combined modality therapy

Optimal treatment for Hodgkin's disease during childhood is unknown. We report the treatment outcome of patients with Hodgkin's disease <13 years of age seen at the American University of Beirut Medical Center (AUBMC) between 1980 and 1996. A retrospective review of the medical records of 24 children treated for HD at AUBMC was performed. Treatment consisted of chemotherapy alone (n = 15) or chemotherapy plus involved field radiotherapy (n = 9). Chemotherapy consisted of COPP, ABVD, or alternating cycles of each for a total of 6 to 12 cycles, depending on clinical and radiological response; three patients received MOPP. Five patients in the chemotherapy group had clinical stage (CS) I and II and 10 had CS III disease. In the combined modality group, eight patients had CS I and II and one had CS IV disease. At a median follow-up of 5 years, the event-free survival (EFS) for the combined modality group was 100% and the overall survival (OS) 100%. For the chemotherapy alone group, the EFS was 56% and the OS was 79%. Four patients (27%) in the chemotherapy alone group who had Stage IIIB disease relapsed. Mean time to relapse was 4.3 years. In our experience, six cycles of COPP or (COPP plus ABVD) alone were suboptimal for the treatment of Stage IIIB Hodgkin's disease patients, especially those with involvement of lower abdominal nodes (III2B), extensive pulmonary disease, or mixed cellularity histology. Radiation therapy or additional chemotherapy courses are required for these patients.     

Predictive value of the early response to chemotherapy in high-risk stages II and III Hodgkin's disease

A series of 60 patients with "high risk" Stage II and III Hodgkin's disease (B symptoms, or large mediastinal mass, or E lung disease) were staged without laparotomy and treated with combined modality treatment: mechlorethamine, vincristine, procarbazine, and prednisone (6 MOPP) plus radiotherapy. Patients were restaged after the first three courses of MOPP and the status of response to therapy at that time was called early response to chemotherapy (ERC). The rate of nitrogen mustard and procarbazine delivery (MRD) during the first three cycles of chemotherapy also was assessed. At the completion of the therapy patients were restaged and the final response was assessed. Fifty-two (86.7%) patients entered complete remission (CR). Forty-eight percent of the complete responders achieved CR in the first three courses of MOPP. Eight-year survival and disease-free survival (DFS) rates of the patients achieving CR were 71% and 73%, respectively. Survival and DFS were significantly better for the patients who achieved CR in the first three cycles of chemotherapy than for patients who entered CR at a later stage of therapy: 8-year survival 90% versus 55% (P = 0.00); 8-year DFS 87% versus 59% (P = 0.01). The attainment of a complete ERC was adversely affected by lymphocyte depletion (LD) histologic type (P = 0.01) and MRD less than 65% (P = 0.04). However, when a multivariate regression analysis was used, ERC was the only significant prognostic variable for survival and DFS and its predictive value was confirmed even after correction by MRD. These data suggest that the rapidity of response to chemotherapy could be an important prognostic factor in high-risk Stage II and III Hodgkin's disease.     

Radiation therapy for pathologic stage III Hodgkin's disease with and without chemotherapy

Ninety-eight patients with pathological Stage (PS) III Hodgkin's disease treated between 1969 and 1984 were retrospectively analyzed. Treatment consisted of radiation therapy (RT) alone in 46 patients and combined radiation therapy and chemotherapy (CMT) in 52 patients. The median follow-up was 10 years (range 3-19 years). Fifteen-year year survival for patients with Stage III1-is better than for Stage III2 patients (82% vs 53%; p = .014). Patients with Stage III1A have a favorable prognosis regardless of treatment modality. The probability of freedom from relapse at 15 years for patients with pathological Stage III1A treated with radiation therapy is 70%, compared to 83% for pathological Stage III1A patients treated with combined modality therapy (p = .56). In patients with pathological Stage III2A, III1B, and III2B relapses were less frequent with the use of combined modality therapy compared to radiation therapy. We conclude that pathological Stage III1A patients may be treated with radiation therapy alone; the other subsets of patients benefit from combined radiation and chemotherapy.     

Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated,advanced breast carcinoma

BACKGROUND: The objective of this study was to evaluate the activity and safety of oral capecitabine in combination with docetaxel and epirubicin (TEX) as first-line treatment for patients with locally advanced/metastatic breast carcinoma. METHODS: This open-label, Phase II study was conducted at six Italian centers. Treatment consisted of epirubicin, 75 mg/m(2) (intravenous bolus), and docetaxel, 75 mg/m(2) (1-hour infusion), both administered on Day 1, plus oral capecitabine, 1000 mg/m(2) twice daily, on Days 1-14 of each 3-week treatment cycle. RESULTS: A total of 67 patients received 392 cycles of treatment, with a median of 6 cycles in patients with Stage III disease (n = 34 patients) and a median of 8 cycles in patients with Stage IV disease (n = 33 patients). The objective response rate was 82%, including complete responses in 21% of patients. A greater proportion of patients with Stage III disease achieved tumor responses compared with patients who had Stage IV disease (97% vs. 67%, respectively). Among 34 patients with Stage III disease, pathologic complete responses were confirmed in 10 patients (29%). TEX chemotherapy demonstrated an acceptable safety profile. There was a low incidence of Grade 3 adverse events, and Grade 4 adverse events were particularly rare (4%). The most common Grade 3-4 adverse event was febrile neutropenia, which occurred in 16% of patients. CONCLUSIONS: TEX combination therapy has important antitumor activity and an acceptable safety profile in this setting. A large, randomized, Phase III trial is ongoing to compare TEX chemotherapy with an epirubicin plus docetaxel regimen in patients with untreated, advanced breast carcinoma.     

Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy

The objective of this analysis was to evaluate the efficacy and treatment outcome of CHOP and CHOP combined with nitrosourea chemotherapy in natural killer (NK)/T-cell lymphoma of the nasal cavity. Sixty-three patients with NK/T-cell lymphoma of the nasal cavity were treated with CHOP or CHOP combined with oral nitrosourea chemotherapy between January 1997 and June 2005. By the Ann Arbor Lymphoma Staging Classification, 57 patients (90%) had Stage IE or IIE disease and six patients (10%) had Stage III or IV disease. All patients with Stage IE or IIE disease were intended to be treated curatively with combined chemoradiation; and patients who had Stage III or IV disease were treated with chemotherapy alone with curative intention. Chemotherapy consisted of: (1) up to six cycles of the standard CHOP based regimen, or (2) up to six cycles of the standard CHOP based regimen with oral Semustine dosed at 120 mg (or Lomustine dosed at 100mg) on day 1 of each chemotherapy cycle. External beam radiation therapy was delivered by daily conventional fractionation by Co-60 or 6MVx linear accelerator for patients with Stage IE or IIE disease. The radiation dose to the tumor bed was between 36 and 50 Gy with a median dose of 45 Gy. Fifty-three patients received chemotherapy prior to radiation, and four patients were treated with involved field radiation before chemotherapy. The median follow up for all 44 surviving patients was 31 months (range: 6-104 months). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively. The PFS and OS of patients who were treated with or without oral nitrosourea in addition to CHOP were 73% vs. 44% (P=0.035) and 75% vs. 64% (P=0.276), respectively. Nine patients with Stage IE or IIE diseases developed disease progression during their planned treatment and died within 10 months after the initiation of treatment; Six patients who achieved complete response (CR) after planned chemoradiation developed systemic recurrence and died at 13-48 months despite salvage treatment; one patient died of Hemophagocytic Syndrome during radiotherapy after achieving CR from chemotherapy. Three patients with Stage III or IV disease died during chemotherapy or during salvage treatment at 2, 4, and 19 months, respectively. Among the 59 patients who received chemotherapy as their initial treatment, 29, 6, 12, and 12 patients had complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) respectively after chemotherapy. The 2-year overall survival rates for these four groups of patients were 100%, 75%, 60%, and 17%, respectively (P<0.0001). Multivariate analysis revealed that International Prognostic Index (IPI) for Lymphoma, perforation of nasal septum as a presenting symptom, "B" symptoms, ECOG performance, as well as response after chemotherapy, were significant independent prognostic factors for this group of patients. The extent of response after induction chemotherapy is significantly related to the treatment outcome of patients with nasal NK/T-cell lymphoma. CHOP based chemotherapy combined with oral nitrosourea followed by involved field radiotherapy may provide improved treatment results compared to conventional CHOP chemotherapy and radiation. This strategy needs to be optimized and tested in a prospective trial for its efficacy.     

Malignant lymphomas of follicular center cell origin in man. VI. Large cleaved cell lymphoma

Between 1970 and 1986 61 patients with large cleaved cell lymphoma (LCCL) were observed and treated. Median age was 56, and there were slightly more women than men (ratio, 1.4:1). Forty-four cases (72%) had both a nodular and diffuse pattern; eight cases were nodular; nine cases were diffuse. Forty-three patients (70%) had Stage III or IV disease; four patients were Stage I (7%); 14 were Stage II (23%). Bone marrow was involved in 15 of 56 evaluable patients (27%). The median survival was 57 months. It was significantly shorter in symptomatic patients (median, 20 months) than in asymptomatic patients (median, 66 months; P = 0.002). Survival time was also shorter in Stage III and IV patients (median, 46 months) compared with Stage I and II patients (median, 100+ months; P = 0.032). Survival was independent of the disease pattern, marrow involvement, age, gender, and surface immunoglobulin heavy or light chain. Among Stage III and IV patients, survival was the same in patients who received therapy initially and in those who were treated expectantly. Among 10 advanced-stage patients who did not initially receive therapy, the median time to beginning therapy was 17 months; five patients received no therapy for 40 to 96 months. Among 14 advanced-stage patients receiving therapy regarded as curative in aggressive lymphoma, 50% experienced a complete remission (CR). However, unlike other aggressive large cell lymphomas, long-term, relapse-free survival was observed in only 9% of patients as the majority of CRs were associated with relapse rather than cure. Despite the fact that it is a large cell lymphoma, LCCL is best regarded as an indolent lymphoma.     

Results of radiation therapy of stage I-II non-Hodgkin's lymphoma localized in the head and neck: Osaka University Hospital experience

A retrospective analysis of 251 patients (stage I: 125; stage II: 126) with non-Hodgkin's lymphoma localized in the head and neck and treated between 1971 and 1985 was performed. Of these, 28 patients (11%) had histology of low-grade malignancy, and 218 (87%) had intermediate malignancy. Waldeyer's ring was the most frequent site of involvements (114 cases), extranodal site (91), and cervical lymph node(s) (46) in the order. Treatment consisted of radiation therapy alone in 173 patients and 78 patients were treated with chemotherapy combined. Local control rates by radiation therapy was 95%. Five-year survival and relapse-free survival rates were 72% and 61%, respectively, in stage I, and 63% and 54%, respectively, in stage II. A brief chemotherapy for 2 cycles followed by local-regional radiation therapy appeared better survival as compared to initial radiation therapy alone.     

Small cell carcinoma of the urinary bladder. The Mayo Clinic experience

BACKGROUND: Small cell carcinoma (SCC) of the urinary bladder accounts for 0.35-0.70% of all bladder tumors. There is no standard approach to the management of SCC of the urinary bladder. METHODS: The authors performed a retrospective study at Mayo Clinic (Rochester, MN) to characterize the clinical and pathologic features of patients with SCC of the urinary bladder diagnosed between 1975 and 2003 with emphasis on management. RESULTS: Forty-four patients were identified who had primary bladder SCC, 61.4% of whom had pure SCC. The male:female ratio was 3:1, the mean age was 66.9 years, and the mean follow-up was 3.2 years. Twelve patients (27.3%) had Stage II disease, 13 patients (29.6%) had Stage III disease, and 19 patients (43.2%) had Stage IV disease. The overall median survival was 1.7 years. The 5-year survival rates for patients with Stage II, III, and IV disease were 63.6%, 15.4%, and 10.5%, respectively. Six of eight patients with Stage II bladder SCC achieved a cure with radical cystectomy. Five patients with Stage IV disease had obvious metastases and received chemotherapy. Fourteen patients underwent radical cystectomy and were diagnosed later with locally advanced disease (T4b) or lymph node metastasis (N1-N3; Stage IV disease). Only 2 of 19 patients with Stage IV disease who received adjuvant chemotherapy were alive at 5 years. CONCLUSIONS: Patients with bladder SCC should undergo radical cystectomy except when metastatic disease is present (M1), in which case, systemic chemotherapy is indicated. Adjuvant treatment is not indicated for patients with Stage II disease after radical cystectomy but should be considered for patients with Stage III and IV disease. Chemotherapy should be a platinum-based regimen.     

Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease.

PURPOSE: To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. PATIENTS AND METHODS: From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV. RESULTS: Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively. CONCLUSION: Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.     

Concurrent radiation therapy, 5-fluorouracil, and cisplatin for stage II, III, and IV, node-negative, squamous cell head and neck cancer. Results and surgical implications.

METHODS. Between 1983 and 1989, 42 patients with Stage II, III, and IV, node-negative, squamous cell head and neck cancer were treated with concurrent 5-fluorouracil, cisplatin, and radiation therapy. Two courses of chemotherapy with 30 Gy of concurrent radiation therapy were to be followed in all patients by definitive surgery and then an additional 30 Gy of radiation therapy and one to two courses of chemotherapy. The patients who achieved a complete response to the initial induction treatment, however, did not undergo surgery. RESULTS. After the completion of all therapy, 41 of the 42 patients (98%) were considered disease-free. Only 4 of these 41 had relapses, for a projected Kaplan-Meier disease-free survival rate of 86%. Treatment failure occurred in no patients with Stage II, 1 of 17 patients with Stage III, and 4 of 14 patients with Stage IV disease. Of the 42 patients, 23 (55%) did not require surgery after achieving a complete response to induction therapy, and only 1 of these 23 patients subsequently had a relapse. CONCLUSIONS. Although the value of adding chemotherapy to conventional treatment remains unproven in squamous cell head and neck cancer, this treatment schedule appears promising in node-negative disease. Randomized trials will be necessary, however, to validate the efficacy of this approach and confirm the suggestion by the authors that surgery can be avoided in most patients with N0 disease.     

PALA, vindesine, and cisplatin combination chemotherapy in advanced malignant melanoma. A pilot study

Twenty-two patients with advanced malignant melanoma were entered in a pilot study receiving combination chemotherapy with PALA, vindesine, and cisplatin (PVP). Treatment consisted of PALA 3000 mg/m2 IV on days 1 and 2, vindesine 3 mg/m2 IV on days 1 and 8, cisplatin 30 mg/m2 IV on days 1 through 5, with treatment cycles repeated on day 21 every 3 weeks. Of 22 patients, 3 had non-visceral disease confined to iuxtaregional tumor growth (Stage III), and 19 had disseminated and/or visceral disease (Stage IV). The male/female sex distribution was 13/9; median age was 45 years. All 22 patients had measurable disease; 21 were evaluable for response and toxicity. Five patients (24%) had a complete response (CR) with a median duration of 5 months, and four patients (19%) had a partial response (PR) with a median duration of 3 months. Seven patients showed disease stabilization (33%) with a median duration of 2 months. Progressive disease was seen in five patients (24%) and was commonly due to widespread visceral disease. CR could be found predominantly in non-visceral disease, whereas PR could be observed in visceral disease also. Survival time from the onset of PVP chemotherapy cannot be estimated finally, since some of the responses are continuing at the present time, and 7 of 21 patients are still alive. Currently, median survival time for responders is 8 months, and for nonresponders, 5 months. Toxicity of PVP chemotherapy is mild to moderate and allows cytotoxic drug administration on an outpatient basis. PVP chemotherapy appears to have significant activity against malignant melanoma and may therefore be an alternative regimen in the management of advanced disease. However, despite the relative high remission rate especially in non-visceral disease, response duration remains disappointingly low.     

Long-term results of combined modality treatment with I-125 implantation for carcinoma of the pancreas.

From 1981 to 1987, 81 patients with localized, unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital with a combination of intraoperative Iodine-125 implantation, external beam radiation, and peri-operative systemic chemotherapy. Fifty patients had Stage II disease and 31 patients had Stage III disease. Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients.     

Long-Term Prognosis after Surgery for Locally Recurrent Rectal Cancer: A Retrospective Study

Objective: Resection is usually recommended for locally recurrent rectal cancer (LRRC) for which R0 resection is possible, but its suitability varies by individual patient risk. Here, we report outcomes of resected LRRC in our hospital. Methods: We retrospectively evaluated short- and long-term results of 33 patients who underwent resections for LRRC from January 2003 to December 2019. Results: At the initial surgeries for these 33 patients, their disease stages at that time were Stage I: n=2, Stage II: n=12, Stage III: n=11, Stage IV: n=6, and unknown: n=2. Patients with Stage IV disease at their initial surgeries underwent radical one-step or two-step procedures. Metastasis to other organs was observed in 5 patients at the their initial LRRC diagnoses. At the LRRC surgeries, 7 patients received palliative surgeries; 26 received intent-to-treat resections, of which 17 were R0 resections. All-grade postoperative complications were observed in 11 patients, including 1 surgery-related death. Five-year overall survival rates were all cases: 38.4%; R0 group: 52.3%, R1 or R2 group: 19.4%, and palliative surgery group: 0%. The R0 group thus had significantly better prognosis than other patients (P = 0.0012). Eleven patients in the R0 group (64.7%) suffered re-recurrences but some patients achieved long-term survival through chemotherapy, radiation therapy, and surgery for metastasis to other organs, even after re-recurrence. Conclusion: Long-term prognosis after surgery for LRRC was significantly better for patients with R0 margins. Multimodal treatments may greatly improve survival for patients who suffer re-recurrences after local recurrence resections.