Remission Rates Following Preoperative Chemotherapy and Radiation Therapy in Patients with Breast Cancer

PURPOSE: To evaluate remission and breast-conservation rates after preoperative chemotherapy or chemo-radiotherapy (CT-RT). PATIENTS AND METHODS: Seventy-three patients with 74 biopsy-proven invasive breast cancers prospectively entered the protocol. Eighteen patients were treated by neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (chemotherapy group). Fifty-five patients with 56 tumors were treated with combined neoadjuvant chemo-radiotherapy, followed by surgery (chemo-radiotherapy group). Most patients of both treatment groups received 4 cycles of EC chemotherapy. In some patients with large tumors 3 cycles of CMF were added. Chemotherapy was followed by hormonal treatment with tamoxifen or LHRH agonists in case of positive hormone-receptor status. Preoperative radiotherapy was administered using 2 Gy fractions up to a total dose of 50 Gy, followed by a tumor boost of 6 to 11 Gy. The median overall treatment time was 41 days (range: 35 to 55 days). The median time interval between end of neoadjuvant therapy and surgery was 11 weeks (range: 10 to 22 weeks) and 27 weeks (range: 11 to 41 weeks) for the chemotherapy- and chemo-radiotherapy group. The median time interval between end of chemotherapy and the beginning of irradiation ranged between 2 and 8 weeks (median 4 weeks) in the chemo-radiotherapy group. RESULTS: Side-effects due to chemo- or radiotherapy were moderate and reversible. In the chemotherapy group 17/18 patients (94%) achieved a partial (pPR) and 1/18 patients (6%) a complete histopathological response (pCR). In the chemo-radiotherapy group 32/56 (57%) showed a pPR and 24/56 (43%) a pCR. The difference in complete remission is significant (Fisher's Exact Test: p = 0.004). In 45/74 cases (61%) the breast was preserved, immediate breast reconstructions with rectus myocutaneous flaps (TRAM) after mastectomy were performed in 8/74 cases (11%) and modified radical mastectomies without reconstruction were required in 21/74 cases (28%). The breast conservation rates were similar in both treatment groups. CONCLUSIONS: Even though the small number of patients in the present protocol does not permit definite conclusions, the results of combined modality treatment seem promising with regard to tumor remission within the treated breast and as a tool for breast conservation in advanced stage disease. On the basis of these encouraging data a prospective Phase-III study has been initiated.     

Unresectable hilar cholangiocarcinoma: combined percutaneous and radiotherapic treatment

PURPOSE: Evaluate, in patients with inoperable hilar CLCA, the efficacy of multimodality treatment (brachiotherapy, chemotherapy, external radiotherapy and endoprosthesis positioning) in terms of survival, quality of life and cost/benefit compared to palliative surgical treatment. MATERIAL AND METHODS: 20 patients with inoperable hilar CLCA were evaluated. Ten were considered for combined palliative and radiotherapy treatment according to the following protocol: percutaneous colangiography followed by positioning of right and left internal biliar drainage (10-12 F); intraductal brachiotherapy using Ir-192 needles was performed (7 Gy). A second administration was after 7 days. Total dose was 14 Gy; the biliar drainages were then replaced by endoprosthesis (12-14 F) and left in position for 3 months in order to model the post-attinic fibrosis and to prevent stenosis; external radiotherapy was administered starting 15 days after last brachiotherapy treatment (26 administrations (180 cGy) in 5 weeks, total 46 Gy); chemotherapy (5 FU: 350 mg/mq/die) for 5 days during the first and the fifth week of external radiotherapy; biliar endoprosthesis were removed by endoscopic and, or transhepatic mode after 3 months from end of therapy, verifying. Cholangiography assessed the patency of the biliar duct. Metallic stents were placed if results were not satisfactory; follow-up was by: hepatic lab work-up, tumoral markers, US or TC evaluated disease progression. RESULTS: In 5 of the 10 patients considered for the combined treatment, 5 patients completed the protocol and 5 were treated only with brachiotherapy because of deterioration of clinical conditions. All patients had initial complete remission of jaundice although it recurred with disease progression that led to death. No acute post-radiotherapy complication was observed. Digestive hemorrhage (chronic post-radiotherapy complication) was the cause of death in one patient. DISCUSSION AND CONCLUSIONS: Good results were observed in the patients that completed the protocol, mean survival was 7,5 months instead of 1,75 months as in patients that underwent only percutaneous drainage. Better results may be obtained taking in consideration the poor clinical conditions of the patients at the time of diagnosis. The proposed therapeutic protocol requires an average hospitalization of 10-15 days instead of 15-20 days as for palliative biliar-digestive deviation, being less invasive and thus associated to lower morbidity and no mortality.     

Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer

Purpose

To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer.

Methods

A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m², day 1) and 5-fluorouracil (1000 mg/m² in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m²).

Results

Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed.

Conclusions

High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer.     

Combined radiotherapy with cis- or carboplatin in advanced head and neck tumors

This report reviews the treatment results of 111 patients with stage T3-4, N0-3, M0, biopsy proven squamous cell carcinoma of the oropharynx and oral cavity. All patients were treated by primary irradiation with 1.8 to 2 Gy per day for five days a week up to a target volume dose of 39.6 or 40 Gy. Simultaneously 20 mg/m2 cisplatin was given under hyperhydration and mannitol diuresis on days 1 to 5. In case of partial tumour regression radiotherapy was continued up to 70 Gy with another course of cisplatin. In case of minor response surgery was interposed followed by subsequent irradiation with 30 Gy and a second course of cisplatin. 67% of the patients showed an initial complete tumour involution and 27% a partial response. The five year actuarial survival rate with a minimum follow-up of two years is 47.6%. More than 96% of the long term survivors showed a complete response after the end of treatment. The results demonstrate that concomitant radiation and chemotherapy with cisplatin is a highly effective treatment in advanced head and neck carcinoma with tolerable toxicity. Carboplatin (CBDCA) is a second generation platinum analog and has shown comparable antitumour activity but less nephro- and neurotoxicity than cisplatin in head and neck cancer. In order to determine the feasibility and efficacy of simultaneous application of CBDCA and radiotherapy a phase I-II study is going on. Between September 1987 and March 1988 30 patients with advanced squamous carcinoma of the head and neck (T3-4, N0-3) have entered this trial. Patients were separated into three groups which received 60 mg/m2. 70 mg/m2 and 80 mg/m2 CBDCA from days 1 to 5 and 28 to 32. Radiotherapy was administered up to a target absorbed dose of 70 Gy. 5 X 2 Gy/week in shrinking field technique. The group which received 80 mg/m2 CBDCA reached the myelotoxicity limit so that subsequent patients were treated with 70 mg/m2. Among 30 patients who completed the treatment, 22 showed a complete (CR) and eight a partial remission (PR). Despite the short follow-up period the preliminary results appear to be comparable with those achieved after combined radiotherapy and cis-DDP application without any limitations for patients with renal or cardiovascular disorders.     

Simultaneous radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in advanced head and neck tumors]

Between 1.1. 1987 and 31.12. 1988 47 patients with locally advanced head- and neck tumours (UICC-stage II: one patient, stage III: 16 patients, stage IV: 30 patients) were treated with simultaneous radio-chemotherapy. Localisations were hypopharynx (23 = 49%), oropharynx (16 = 34%) and other sites (8 = 17%). Radiation therapy consisted of 60 Gy (primary region, N+) or 50 Gy (N0) in daily fractions of 2 Gy each over six weeks. During week 1 and 5 of radiotherapy two courses of chemotherapy with 5-FU (600 mg/m2/day, i.v. continuous infusion for five days) and cis-platin (25 mg/m2/day i.v. bolus for five days) were administered. 43/47 patients (91%) responded to therapy. 34/47 (72%) patients achieved a complete remission, 9/47 (19%) a partial remission, and 4/47 (9%) no change. With a minimum follow-up of 26 months 17/47 patients (36%) are alive and NED, 4/47 (9%) are alive with tumour. 18 patients (38%) died of cancer, eight patients (17%) died of second tumours, intercurrent diseases and of unknown reasons. Actuarial four-year survival is 45% (stage III: 56%, stage IV: 42%), four-year NED survival is 35% (stage III: 68%, stage IV: 18%). There were no loco-regional recurrences after additional surgical treatment of the primary and the neck following complete remission. In contrast after RCT alone and complete remission local recurrences in 6/21 patients (29%) and regional recurrences in 5/24 patients (21%) occurred. We conclude that simultaneous RCT is a new very effective treatment modality of locally advanced head and neck tumours producing superior loco-regional control compared to conventional management.     

Intravenous mitoxantrone use and simultaneous radiotherapy as a palliative treatment in recurrent head and neck tumors]

After preceding radiotherapy, chemotherapy and/or surgery the therapeutic options are limited in case of recurrence. In order to enhance the effect of a reduced radiation dose we have combined intravenous mitoxantrone and simultaneous irradiation. From 1988 to 1991 22 patients with recurrent head and neck carcinomas were treated with this combined regimen. 20 patients had already been irradiated with 50 to 70 Gy. The second treatment course was given with 19.8 to 56.0 Gy and simultaneous application of one to three courses of mitoxantrone. Eleven (50%) patients achieved a clinical complete remission. A partial remission was seen in nine patients.     

Fractionated and hyperfractionated total body irradiation in the conditioning of allogenic bone marrow transplant in acute lymphatic leukemia. Results

Two different Total Body Irradiation (TBI) regimens were employed (1981 to July 1983) in Genoa in the conditioning program for the allogeneic Bone Marrow Transplantation (BMT) of 22 patients suffering from Acute Lymphoblastic Leukemia (ALL) in remission (7 patients in 1st remission, and 15 in 2nd remission). All patients were treated with Cyclophosphamide -60 mg/kg administered for two consecutive days (day -7 and -6)--and subsequently underwent fractionated TBI (days -3, -2, -1), that is, our conventional TBI regimen: 3.3 Gy/day per 3 days (total dose: 9.9 Gy). From August 1983 through 1988, 33 patients (14 in 1st remission and 19 in 2nd remission) were given 2 Gy twice a day, 6 hours apart, for 3 consecutive days (total dose: 12 Gy). Cyclosporine A was used for GvHD prophylaxis. At 58 months, out of the total figure of ALL patients in 2nd remission, 19% of those treated with 9.9 Gy/3 fr/3 days (fractionated TBI) is likely to be in remission, versus 65% of the cases treated with 12 Gy/6 fr/3 days (p less than 0.01) (hyperfractionated TBI); the actuarial overall survival is 23% after fractionated vs 60% after hyperfractionated TBI (p = 0.05). The incidence of idiopathic interstitial pneumonitis was very low (3.6%). Thus, we conclude that, in ALL patients in second remission, hyperfractionated TBI (12 Gy/6 fr/3 days) yields better results than fractionated TBI (9.9 Gy/3 fr/3 days), with lower relapse rate (33% vs 83%) and higher survival.     

Results of whole lung irradiation and chemotherapy in comparison with partial lung irradiation in metastasizing, undifferentiated soft tissue sarcomas

The poor prognosis of patients with unresectable pulmonary metastases of soft tissue sarcoma is well known. In order to evaluate the beneficial effect of radiotherapy, we have treated 44 patients with pulmonary metastases of grade 3 soft tissue sarcoma from 1980 to 1986. In 36 patients the treatment volume was restricted to the single metastases up to a dose of 50 to 60 (9 to 10 Gy/week). The survival rate at one year was 18% and at two years 6%. Eight patients were treated with a combined regimen, consisting of cisplatin and ifosfamide with simultaneous whole lung irradiation. Irradiation was performed with 8 or 16 MV photons at a hyperfractionation of 2 x 0.8 Gy/day (8 Gy/week). After a dose of 12 Gy, the single metastases were boosted up to 50 to 60 Gy, with a second course of chemotherapy. In six of eight patients complete remissions were achieved, one patient showed a partial remission. The survival rate at 27 months was 50%. The patients with partial remission died from pulmonary progression at 23 months. One patient died after twelve months from a loco-regional recurrence in the tonsillar fossa without evidence of pulmonary disease. Side effects included alopecia and moderate bone marrow suppression approximately twelve days after each chemotherapy cycle. Pulmonary fibrosis was observed only at the high dose volume without impairment of respiratory function. From these observations the conclusion is drawn that whole lung irradiation simultaneously with cisplatin and ifosfamide chemotherapy provides good palliative results without relevant morbidity in patients with high grade unresectable pulmonary metastases of soft tissue sarcomas.     

同期化疗并后程加速超分割放疗食管癌的毒副反应

目的观察同期化疗并后程加速超分割放疗食管癌耐受性和毒性反应。方法选择病变长度≤12cm、无远处转移证据（锁骨上淋巴结转移除外）的中晚期食管癌分同期化疗并后程加速超分割放疗（后超组）和同期化疗并常规分割放射治疗（常规组）各40例。两组化疗方案相同：顺铂20mg／m^2、氟脲嘧啶脱氧核苷500mg／m^2、每周2次，共6次。后超组放疗第1～28天，为常规分割放疗，40Gy，分20次，共28d；第29～42天，缩野后行加速超分割放疗，1．5Gy，次，2次，d，共27Gy，分18次，共13d，总剂量：67Gy，分38次，共42d。常规组放疗为全程常规分割放疗，总剂量为70Gy，分35次，共49d。结果急性放射性食管炎的发生率后超组为100％，常规组为87．5％；其中Ⅲ、Ⅳ级食管炎的发生率后超组为35％，明显大于常规组15％（P〈0．05），且持续时间长。白细胞下降、胃肠道不良反应、放射性肺炎及肺纤维化两组比较，其差异无统计学意义（P〉0．05）。后超组有3例、常规组有1例因Ⅲ级食管炎而使疗程中断，经抗生素和激素等对症治疗后均在7d内恢复放疗。结论①同期化疗并后程加速超分割放疗的放射性食管炎虽有所增加，但多数患者能耐受；②骨髓抑制、胃肠道反应、放射性肺炎及肺纤维化两组比较差异无统计学意义。     

三维适形放射治疗联合化疗治疗局限期小细胞肺癌的疗效分析

目的 回顾性分析85例局限期小细胞肺癌三维适形放疗(3D-CRT)联合化疗疗效及生存率,探讨局限期小细胞肺癌的放疗方法。方法 2004年3月至2008年6月经病理或细胞学证实,且进行4个及以上周期化疗联合放疗的局限期小细胞肺癌85例,采用基于CT定位的累及野放疗, 6~10 MV X射线,剂量为46~66 Gy,中位剂量50 Gy,1次/d,5次/周,5~7周。结果 全组患者完全缓解率36.5%,部分缓解率52.9%,稳定率10.6%;有效率89.4%。全组患者1、2、3年总生存率分别为65.9%、33.8%、15.9%,总中位生存时间18个月。59例患者有治疗失败原因记录,局部复发9例占15.2%,局部复发+远处转移21例占35.6%,远处转移29例占49.2%。结论 局限期小细胞肺癌三维适形技术累及野照射疗效较好,需进一步扩大病例数。     

Follow-up data of our pilot study on concomitant hyperfractionated radiotherapy and cisplatinum (CDDP) in patients with advanced cancer of the head and neck.

Since 1988, 52 patients with stage III/IV squamous cell cancer of the head and neck have been treated by concomitant irradiation with 2 x 1.2 Gy/d on five days per week up to a total dose between 72 and 76.8 Gy without split and 5 x 20 mg/m2 cisplatinum (CDDP) as short infusion finished approximately 30 min before the second session on five days of the first and the fifth week of radiotherapy. Radiotherapy has been suspended after 30 and 50 Gy in three patients for insufficient response. In all other patients, radiotherapy has been completed. Due to a slow haematologic recovery, 34% of the patients received only one cycle of CDDP Grade 3 mucositis, occurring during radiotherapy in all patients, healed in a couple of weeks after radiotherapy. Three patients have a persisting ulcer between eight and 36 months after radiotherapy with biopsies negative for tumour and also no other signs of tumour. The ulcers are situated in the region of the former primary tumour with an extensive destruction of tissue already before radiotherapy (cumulative risk of this complication after three years 8%). There were no other major complication. Cumulative local control after three years was 67% (75% including salvage surgery in two patients) with a plateau after twelve months. Total survival after three years was 62%. For the whole follow-up period, local control in the region of the primary tumour after radiotherapy was: 19/29 (T4), 10/15 (T3), 7/10 (T1 + 2, including salvage surgery: 8/10). Local control in the region of the nodal metastasis after radiotherapy was: 5/14 (N3, including salvage surgery: 6/14). 18/21 (N2) and 6/8 (N1).     

Remission Rates in Breast Cancer Treated with Preoperative Chemotherapy and Radiotherapy

PURPOSE: Evaluation of remission rates after neoadjuvant chemotherapy alone or followed by preoperative radiotherapy. PATIENTS AND METHODS: 194 women with 198 biopsy-proven breast tumors were evaluated in this retrospective study. Of the 198 cases evaluated, 64 received neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (CT group). In 134 cases, sequential preoperative chemo-/radiotherapy (CT-RT group) was given. In both groups, endocrine treatment was initiated in case of positive hormone receptor status after chemotherapy. The whole breast was homogeneously irradiated using 2-Gy fractions up to a total dose of 50 Gy, followed by a boost of 6-11 Gy to the tumor. RESULTS: A histologically proven complete remission (pCR) was achieved in 3% (2/64) in the CT and in 42% (56/134) in the CTRT group. The logistic regression analysis, including clinical tumor category (cT), lymph node (cN) and metastasis status (cM), grading (G), hormone receptor status (HRS), number of preoperative chemotherapy cycles, preoperative tumor volume, and preoperative radiotherapy, revealed that HRS (p = 0.0232) and radiotherapy (p < 0.0001) were significant factors for achieving pCR. CONCLUSION: Combination of neoadjuvant chemo-/radiotherapy results in significantly higher rates of complete remission than neoadjuvant chemotherapy alone. The significance for tumor-free and overall survival has to be evaluated.     

吉西他滨联合5-氟尿嘧啶和四氢叶酸治疗晚期胰腺癌的临床研究

目的　评价 5 氟尿嘧啶和四氢叶酸联合化疗与加用吉西他滨后治疗晚期胰腺癌的疗效和不良反应 ;以及 5 氟尿嘧啶药物代谢动力学指标的改变。方法　 43例晚期胰腺癌患者分为实验组 ( 2 2例 )和对照组 ( 2 1例 )。实验组 :吉西他滨 10 0 0mg/m2 ,第 1,8,16天静脉滴注 ,5 氟尿嘧啶 40 0mg/m2 和四氢叶酸 10 0mg/m2 于第 1～ 5天静脉滴注 ;对照组 :5 氟尿嘧啶 40 0mg/m2 和四氢叶酸 10 0mg/m2 在第 1～ 5天静脉滴注 ,均以每 4周为 1疗程 ,持续 4个疗程。结果　实验组完全缓解 (CR) 1例 ( 4 .5 %) ,部分缓解 (PR) 6例 ( 2 7.3 %) ,临床受益反应率 (CBR)为 68.2 %;对照组无CR ,PR3例 ( 14 .3 %) ,CBR有效率 3 3 .3 %。实验组出现不良反应的数量和严重程度较对照组提高且差异具有显著性。实验组 5 氟尿嘧啶血浆药物浓度、血浆峰值提高 ,血浆半衰期延长。结论　吉西他滨与 5 FU、四氢叶酸联合应用治疗晚期胰腺癌有一定的客观疗效 ,可明显改善患者的生存质量 ,但不良反应也随之提高。上述变化与吉西他滨改变 5 FU的药物代谢动力学有关     

Concomitant pelvic irradiation, 5-fluorouracil and mitomycin C in the treatment of advanced cervical carcinoma

This was a Phase II study of 24 late (FIGO) Stage IIb and 39 Stage III patients. External beam radiotherapy was given daily, five days a week, using 15 x 15 cm parallel opposed pelvic fields. The first 20 patients had 45.00 Gy mid-plane dose in 20 fractions, Days 1-28, the last 43 patients had 50.40 Gy in 28 fractions, Days 1-43. This was followed by an intracavitary boost of 17.00 Gy to Point A in two fractions over seven days. The first seven patients had concomitant 5-fluorouracil (5FU) 1 g/m2/day (maximum 1.5 g/day) Days 2-5, 30-33 and 57-60, with mitomycin C 10 mg/m2 (maximum 15 mg) Days 2 and 57. Two patients had WHO Grade 4 cytopenia, and only two were able to have full dose intensity. The 5FU dose was reduced to 0.8 g/m2/day, for Days 2-5 and 30-33; mitomycin C was given on Day 2 only. Treatment morbidity with the reduced chemotherapy intensity was comparable with that of radiotherapy alone. Median follow-up was 16 months (range 6-44). Median survival was 35 months. The results were compared with historical controls treated using the same radiation method alone. Two-year survival for late Stage IIb patients was 67% with the combination and 72% with radiotherapy alone; for Stage III, 67% and 49% respectively. Two-year pelvic control for late Stage IIb was 87% (combination) and 84% (radiotherapy alone) and for Stage III, 61% and 55% respectively. In contrast to reports from other centres, these results do not show an overall significant improvement on radiotherapy alone. A Phase III study may not be practicable.     

支气管动脉化疗栓塞结合同步放疗、静脉化疗治疗中心型肺癌

目的探讨支气管动脉化疗栓塞结合同步放疗、静脉化疗治疗中心型肺癌的疗效。方法178例中晚期中心型肺癌患者采用支气管动脉化疗栓塞,第2天行放疗。放疗总剂量60～70 Gy,6～7周完成。3～4周后采用长春瑞滨、顺铂或伊托铂苷、顺铂方案,共化疗2个周期。结果患者临床症状均有明显好转。CR 39.89%,PR 46.06%,有效率(CR+PR)85.95%,中位生存期为23.4个月,1、2、3年生存率分别为79.7%、45.3%、24.5%。无严重并发症发生。结论经支气管动脉化疗栓塞结合放疗、静脉化疗治疗中心型肺癌能延长患者的中位生存期,提高患者的生存率,具有较好的临床疗效。     

Prognostic factors in the treatment of inoperable orofacial tumors with simultaneous radiotherapy and intra-arterial chemotherapy

Between January 1973 and April 1982 66 evaluable patients with advanced inoperable orofacial tumours underwent intraarterial Bleomycin and Methotrexate with simultaneous radiotherapy in a prospective study. 32 patients had no previous treatment, 34 patients had initial surgery, radiotherapy and/or chemotherapy. 15 mg Bleomycin were administered through a catheter into the arteria externa carotis daily in the morning. 25 mg Methotrexate were given in the same way at night followed by 3 mg Calcium-Leucovorin i.m. every 8 hours. The cumulative dose was 300 mg Bleomycin and 500 mg Methotrexate. Four hours after the administration of Bleomycin the target volume was irradiated (single fraction 2 Gy, total dose 60 to 65 Gy). The overall response rate was 65% containing 17% complete and 48% partial remission. Destruction of the bone appeared to be the most important index at the start of the therapy. Further prognostic determinants as previous treatment, localisation of the primary tumours (maxilla and mandibula respectively oral cavity and oropharynx) and local regional lymphnode stage missed statistically significance in the survival time, may be due to a possible radiosensitizing effect of the simultaneous chemotherapy. Complete remission turned out to be the most important prognostic factor after the end of treatment. Patients responding with complete remission show a median disease free survival of 56+ months and a median survival time of 82 months. Acute reactions were reversible. Only in 14% of the patients the treatment could not be finished. Better results could be obtained by electron-affinic radiosensitizers and high LET radiation.     

An original accelerated radiotherapy schedule in stage III to IV head and neck cancers. Results in a multicenter setting.

BACKGROUND: Accelerated radiotherapy delivery has recently been shown to be effective in overcoming repopulation during fractionated radiotherapy. The therapeutic ratio may be particularly favorable for 5-week regimens. This study reports the feasibility and results of a particular accelerated schedule in Stage III to IV head and neck carcinomas used in a multicenter setting. PATIENTS AND METHODS: Seventy-four patients with Stage III (26 patients) or IV (48 patients) head and neck carcinomas were treated with a 5-week accelerated schedule (69.6 to 69.8 Gy in 41 to 40 fractions over a period of 35 to 36 days). Treatment began with 20 Gy in 10 daily fractions to initial involved sites, followed by bi-fractionated radiotherapy (2 x 1.6 Gy to 1.66 Gy/day) to a larger head and neck volume. Thirty-six (49%) patients received induction chemotherapy (median 3 cycles, range 1 to 4 cycles). RESULTS: Grade 3 or 4 (RTOG) confluent mucositis was observed in 57 patients (77%) and Grade 3 dysphagia in 33 patients (44%). Grade 3 or 4 (RTOG-EORTC) late complications were scored in 10.5% of cases. The 5-year actuarial locoregional control rate was 56% (95% CI: 42 to 71). The 5-year overall actuarial survival was 32% (95% CI: 18 to 46). Induction chemotherapy was not associated with a more favorable outcome. CONCLUSIONS: This study demonstrates the feasibility of this schedule in a multicenter setting. The oncologic results appear similar to those obtained by other accelerated regimens, while the rate of late complications seems acceptable. Five-week accelerated regimens warrant further evaluation, particularly in conjunction with concomitant chemotherapy, in the framework of prospective trials.     

Pulmonary complications of multimodality therapy for esophageal carcinoma

Thirty patients with cancer of the esophagus were treated with multimodality therapy. We studied the incidence of pulmonary complications in these patients. The value of chest radiographs and sequential measurements of carbon monoxide diffusing capacity (DLco) in predicting pulmonary toxicity was determined. Patients were divided into two groups, according to treatment. Patients in group I (n = 16) received two cycles of chemotherapy (bleomycin 15 units/m2, cisplatinum 120 mg/m2, vincristine 2 mg) and radiotherapy (50 Gy). Based on the presence of interstitial lesions on chest radiographs in five patients the incidence of pulmonary toxicity was 32%. In four of these five patients such an appearance was preceded by a drop in DLco: this was documented in 8 of the 16 patients. Nine patients of group I underwent esophagectomy and four (44%) developed adult respiratory distress syndrome (ARDS). In group II (n = 14) the tumor was resected without other treatment and four (29%) of these patients developed ARDS. The incidence of ARDS in both groups demonstrates that pulmonary complications are mainly related to surgical manipulation and to preexisting lung disease. Preoperative radiotherapy and chemotherapy may be associated factors. Sequential measurements of DLco are more sensitive for detecting pulmonary damage than chest radiographs and should be used to predict pulmonary toxicity.     

Gemcitabine Concurrent with Thoracic Radiotherapy after Induction Chemotherapy with Gemcitabine/Vinorelbine in Locally Advanced Non-Small Cell Lung Cancer

PURPOSE: To determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m(2)) and vinorelbine (30 mg/m(2)) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [(18)F] fluorodeoxyglucose positron emission tomography-(FDG-PET-)based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m(2). The dose of gemcitabine was increased by 100 mg/m(2) until the MTD was realized. Three patients were enrolled for each dose level. RESULTS: Dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m(2), due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. CONCLUSION: After induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m(2) every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy.     

Radiotherapy for High-Grade Gliomas

BACKGROUND AND PURPOSE: The publication of Radiation Therapy Oncology Group (RTOG) Study 83-02 in 1996 stimulated further investigations of altered fractionation, i. e., application of more than one fraction per day, in high-grade gliomas. This review summarizes the results of trials published between January 1997 and June 2002. MATERIAL AND METHODS: To identify suitable trials, a Medline search was performed by use of the following key words: brain tumors/astrocytoma/glioma/high-grade glioma/malignant glioma/glioblastoma multiforme and accelerated radiotherapy/hyperfractionated radiotherapy/altered fractionation. In addition, the search was extended to reference lists of articles and textbooks. Whenever possible, data were extracted from the original papers on an intention-to-treat basis, i. e., patients with protocol violations were not excluded for the purpose of this analysis. Studies in brain stem gliomas, pediatric patients and studies which achieved acceleration by radiosurgery, stereotactic radiotherapy, or brachytherapy rather than conventional external-beam treatment were not included. An exploratory analysis of 2-year survival was also performed. For this purpose, the 2-year survival rate was extracted from each individual study. The total number of 2-year survivors was then calculated for each treatment strategy and compared by use of the chi(2)-test. RESULTS: The authors identified 1,414 patients from 21 studies; two of these were randomized phase III studies. In seven studies (658 patients), chemotherapy or radiosensitizers were not administered in addition to radiotherapy. The others provide a very heterogeneous set of data, because a large variety of drugs and administration schedules was used. Seven studies included patients with glioblastoma multiforme only, two were limited to patients with anaplastic gliomas. Dose per fraction was 1.2-1.8 Gy in 17 studies and 1.9-2.65 Gy in four. Overall treatment time was 12-31 days, except for one study. Three out of five studies where three fractions per day were administered, included a 2-week break (split-course studies). None of the studies reported a significant improvement in survival by altered fractionation in comparison to either institutional historical controls or their respective randomized control arm. Doses of 60-70 Gy do not appear to improve survival compared to 50-60 Gy. The current data provide no arguments for use of three instead of two fractions per day. Median survival was 10 months after radiotherapy alone (658 patients) and 11 months after combined treatment (756 patients). Regarding 2-year survival rates, radiotherapy alone resulted in 13%, combined chemoradiation or use of sensitizers in 23% (p < 0.0001). However, prognostic factors such as tumor histology were not equally distributed and favor the combined-treatment group. Evaluation of six studies of conventional radiotherapy alone resulted in data from 571 patients. Their median survival was 10.8 months. Cumulative 2-year survival amounted to 15%. The studies of conventional radiotherapy plus chemotherapy or sensitizers included 1,115 patients with a median survival of 11 months (2-year survival rate 18.5%). CONCLUSION: Altered fractionation shortens the overall treatment time for adult patients with supratentorial high-grade gliomas. However, there is no significant survival improvement.