Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation. Received: 15 December 1996 / Accepted: 25 March 1997     

Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

放、化疗同步与非同步治疗Ⅲ期非小细胞肺癌的对比观察

目的:为比较放、化疗同步治疗与非同步治疗肺癌的临床效果.方法:选择不手术的Ⅲ期非小细胞肺癌(NSCLC)患者81例,随机分为同步治疗组(42例)和非同步组(39例).结果:治疗总有效率同步组66.7%,非同步组61.5%,前者略高于后者,两者比较无显著差异(P>0.05),但达到上述有效率所用的时间前者平均69天,后者为143天,两者比较有非常显著差异(P<0.01).结论:同步组的近期疗效似优于非同步组,且前者治疗周期、住院周期缩短,更有利于患者康复.     

61例喉癌单纯放射治疗临床分析

目的喉癌单纯放疗效果分析。方法６１例喉癌，以６０Ｃｏ外放射治疗，常规照射。结果五年生存率，声门癌６５％，声门上型癌２４．４％。结论推荐剂量，声门癌Ｔ１Ｔ２６０００ｃＧｙ，Ｔ３６８００ｃＧｙ。声门上型癌Ｔ１Ｔ２６０００～６５００ｃＧｙ，Ｔ３７０００ｃＧｙ。     

76例乳腺癌术后放疗

 从1985年1月～1990年1月，我们对76例乳癌术后患者进行了放疗。Ⅱ期54例、Ⅲ期18例、Ⅳ期4例。放疗采用60钴γ线或6mv一x线、10～12mev电子线。照射胸壁、内乳、锁骨上、腋下等区域。放疗剂量45～50Gy/4.5～5周，5年生存率Ⅱ期80.6％（25/31）、Ⅲ期33.3％（3/9）、Ⅳ期25％（1/4）。我们认为放疗对Ⅱ期以上的患者可降低复发率、提高生存率     

Enhancement of Radiation Response by Paclitaxel in Mice According to Different Treatment Schedules

Purpose: The aim of our study was to determine if paclitaxel could be used as a radiosensitizer in vivo.

Materials and methods: Paclitaxel was tested as a single agent and combined with an X-ray treatment. Paclitaxel was administered i.p. in doses from 30 to 120 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma. Tumor growth delay (TGD) or tumor control dose (TCD₅₀, radiation dose needed to induce local tumor control in 50% of irradiated animals) and moist desquamation dose (MDD₅₀, radiation dose needed to induce serious moist desquamation in 50% of the non-tumor-bearing feet) were the endpoints. DNA flow cytometric analysis was performed.

Results: DNA analysis demonstrated a G2/M block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h from paclitaxel administration. Administering paclitaxel, in graded doses, 15 min before a 10-Gy X-ray treatment resulted in a linear regression line, almost parallel to that with paclitaxel alone, with a growth delay of about 6 days. In contrast, varying the X-ray dose with a constant paclitaxel injection (45 mg/kg b.w.) treatment showed some degree of synergism as the linear regression curves diverged. Interval time and sequence between paclitaxel administration and a 10 Gy X-ray treatment did not influence TGD. Protocols with paclitaxel at 30, 45, or 60 mg/kg were combined with radiation treatments at various doses (from 10 to 65 Gy). Values of TCD50 varied from 50.8 Gy for X-ray alone to 31.8 Gy for paclitaxel 60 mg/kg + X-ray. No differences were observed among MDD of different protocols.

Conclusions: These results suggest that, under some conditions, paclitaxel combined with radiation can show superadditive effects and this result combined with the lack of severe normal tissue damage indicate that a favorable therapeutic gain can be obtained.     

Daily CT localization for correcting portal errors in the treatment of prostate cancer

Introduction: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer.

Methods and Materials: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV₁) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV₁). The prostate or prostate and seminal vesicles (GTV₂) then received 56 Gy to PTV₂. All doses were delivered in 2-Gy fractions.

After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV₃) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field.

Results: Utilizing CT–CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm.

Conclusion: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.     

A change in treatment process with a modern record and verify system

Purpose: With the introduction of new treatment devices, such as a multileaf collimator (MLC) and dynamic wedge (DW), therapists have an increased responsibility to ensure correct treatment. Simultaneously, three-dimensional treatment planning (3DTP) has led to an increased number of portals and table movements. To counteract this challenge and maintain efficiency, a comprehensive record and verify (R&V) system is mandatory. We evaluated a commercial system (Varis) for reliability, ease of use, efficiency, and integration with our planning systems.

Methods and Materials: Some key elements of the Varis system are: integration of MLC and DW; auto setup for MLC, jaw, collimator, gantry, and limited table parameters; direct download of simulation beam data; and a regimented field scheduling system that prescribes all beam data for particular fractions. Evaluation of the system was driven by treatment time analysis, error rates, and an increased workload. These issues were governed by how we disseminated duties and how the system accommodated or changed our processes.

Results: Most data entry is performed by our dosimetry staff. Data can be downloaded from the simulator, but more patients now move from CT simulation and/or 3DTP to the treatment machine. Varis does not link to these systems. The physics staff confirms all entries to correct data entry errors. The workload for dosimetrists increased by an average of 8 minutes/patient entry; physics time increased by 7 minutes/patient entry; the weekly electronic chart check takes approximately 3 minutes/patient. Therapists who used Varis efficiently showed a slight decrease in treatment times, attributed to MLC integration and auto-setup. Some therapists experienced a decrease in efficiency, because of unfamiliarity and excess intervention. On a positive note, notable events have decreased by a factor of 10 since full initiation. Unfortunately, the remaining errors are often the result of a therapist relying on incorrect electronic information.

Conclusion: The Varis R&V system has had an impact on our clinic’s process and efficiency. Checking of all beam data and related field scheduling have helped reduce errors and misconceptions. We feel a dual-energy machine can be operated with two experienced therapists and an up-to-date R&V system more accurately and efficiently than with three therapists working without an integrated R&V. We anticipate future Varis releases will further promote efficiency and accuracy.     

Radiation therapy in the management of desmoid tumors

Purpose: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery.

Methods and Materials: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods.

Results: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05).

Conclusions: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.