Incidental versus symptomatic venous thrombosis in cancer: a prospective observational study of 340 consecutive patients.

BACKGROUND: The clinical significance of incidental venous thrombosis (IVT) is uncertain. The objective of this study was to compare the clinical characteristics and the outcome of cancer patients with IVT with those of patients with symptomatic venous thrombosis (SVT). PATIENTS AND METHODS: Prospective observational study enrolling consecutive cancer patients newly diagnosed with venous thromboembolism (May 2006-April 2009). Diagnosis of IVT was based on vascular filling defects in scheduled computed tomography scans in the absence of clinical symptoms. Anticoagulant therapy was routinely prescribed regardless of SVT or IVT. RESULTS: IVT was diagnosed in 94 out of 340 (28%) patients. Patients with IVT were older (63.7 ± 10.5 versus 60.8 ± 10.5 years, P = 0.035), more frequently had metastatic cancer (82% versus 65%, P = 0.01) and were less likely to be receiving chemotherapy at the time of the thrombotic event (53% versus 67%, P = 0.018). Mean follow-up was 477 days. A lower risk of venous rethromboses was observed in patients with IVT (log-rank P = 0.043), with no differences in major bleeding and overall survival compared with SVT patients. CONCLUSIONS: A high proportion of venous thrombotic events in cancer patients are diagnosed incidentally during scheduled imaging. Prospective controlled trials evaluating the optimal therapy in this setting are required.

Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.

PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.

Role of boost radiotherapy for local control of pure ductal carcinoma in situ after breast-conserving surgery: a multicenter, retrospective study of 622 patients.

PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Management of breast ductal carcinoma in situ in Catalonia, Spain: Results from the Grup Oncologic Calalà-Occità-Catalonia survey with 9-year follow up.

INTRODUCTION: Reliable data on DCIS incidence and management are not available in many countries. The present study describes the management of DCIS in Catalonia, Spain in the year 2005 and compares these findings to data obtained in France. Local recurrence and late toxicity rates from 2005 through the end of 2014 are reported. MATERIALS AND METHODS: Observational survey of patients with pure DCIS (n = 270) diagnosed during 2005. A written questionnaire, the same as used in the French survey, was completed by 14 doctors at 12 cancer centres in Catalonia, Spain. RESULTS: Median patient age was 55 years (range, 29-89). Diagnosis was mammographic in 225 cases (83.3%). Treatment approaches included: mastectomy (10.4% of cases), breast-conserving surgery (BCS) alone (3.7%), and BCS plus radiotherapy (RT) (85.5%). Sentinel node biopsy and axillary dissection were performed in 27.4% and 5.6% of patients, respectively. Hormonotherapy was prescribed in 45.2% of cases. Tumour nuclear grade was as follows: low (16.7% of cases), intermediate (23%), and high (55.6%). Excision was complete (margins ≥1 mm) in 75% of patients treated with BCS alone vs. 95.7% for BCS+RT. The treatment approach varied widely: mastectomy rates ranged from 7.1% to 26.7% of centres, BCS+RT from 55.5% to 87.8%, and hormonotherapy from 3.3% to 83.3%. At a median follow-up of 102.6 months, 14 patients (5.6%) presented ipsilateral breast tumour recurrence. CONCLUSIONS: These findings on DCIS management in Catalonia are consistent with previous international reports. The inter-centre differences observed are similar to those reported in other international surveys during the same period.

Impact of radiotherapy on local control and survival in uterine sarcomas: a retrospective study from the Grup Oncologic Català-Occità.

PURPOSE: In order to provide more information for the clinician and to analyze the impact of radiation therapy on the loco-regional disease-free interval (LRFI), disease-free interval (DFI) and specific overall survival (OS), a multicentric retrospective study of uterine sarcomas has been undertaken using cases reported to the Grup Oncològic Català-Occità (GOCO). PATIENTS AND METHODS: One hundred three patients were selected for this study with a median follow-up period of 49 months. Patients were restaged using the FIGO classification for endometrial adenocarcinoma. Radiotherapy was administered postoperatively to the entire pelvis in 52% of cases (54/103) and was combined with brachytherapy in 24 patients. Mean given dose was 48 Gy, with a 95% confidence interval of 45 to 50 Gy. Variables have been tested for homogeneity between hospitals. Univariate and multivariate analyses have also been carried out. RESULTS: Mean age of the selected patients was 59 years (range 35-84). Stages were distributed as follows: 66 patients (64%) in Stage I; 16 in Stage II (15.5%); 12 in Stage III (11.5%); 9 patients in Stage IVa (9%). Pathological distribution was 41.5% leiomyosarcoma, 39% mixed Mullerian tumours, 16.5% stromal sarcomas, and 2.9% of a miscellaneous group. Overall survival for the entire group was 63.7% and 56% at 2 and 5 years, respectively. Probability of LRFI reached 59.8% at 2 years and 57.4 at 5 years. The DFI at 2 and 5 years were 52.9 % and 48.7%, respectively. The LRFI probability was 41% and 36% at 2 and 5 years, respectively, without radiotherapy and reached 76% at 2 and 5 years among those patients treated with radiotherapy. There was also an increase in DFI probability because of the effect of radiotherapy, from 35% to 68.5% and from 33% to 53% at 2 and 5 years, respectively. The overall survival probability for patients treated with radiotherapy was 76% and 73% at 2 and 5 years, respectively and 51% at 2 years and 37% at 5 years without radiotherapy. Multivariate analysis demonstrated that radiotherapy improved LRFI, DFI, and overall survival. CONCLUSION: We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on loco-regional and disease-free progression intervals and survival.

Induction chemotherapy with cisplatin, bleomycin and methotrexate in advanced head and neck cancer--lack of therapeutic gain.

Seventy patients with stage IV head and neck cancer were treated by two courses of induction chemotherapy followed by surgery plus postoperative irradiation (7) or radical radiotherapy (62). One patient renounced to further treatment after chemotherapy. Each chemotherapy course consisted of methotrexate (40 mg/m2 days 1 and 14), bleomycin (10 mg/m2 days 1, 7 and 14), and cisplatin (50 mg/m2 day 4). Three patients did not complete the two courses of chemotherapy planned due to bad tolerance whereas the rest of the patients tolerated chemotherapy well. 2 CR (3%) and 35 PR (50%) were achieved for an overall response rate to chemotherapy of 53%. 35 (50%) CR were achieved with the whole treatment schedule. The 5-year disease-free survival is 26% for the whole group of patients. The prior response to chemotherapy neither influenced the complete responses to treatment nor the relapse-free survival. The addition of this chemotherapy to conventional treatment was of no value.

Quality assurance of interstitial brachytherapy technique in lip cancer: comparison of actual performance with the Paris System recommendations.

This study takes a quality assurance approach to assessing staff application of Paris System recommendations for brachytherapy. Between 1988 and 1992, 72 patients were treated with brachytherapy for cancer of the lip at Hospital Clinic in Barcelona. Because of the relatively high number of total local recurrences (11%) and the fact that several radiotherapists had come from other hospitals to join the staff, we analysed the technique actually used compared with the recommendations of the Paris System. Results indicate our staff did not, in fact, use the active length prescribed by the Paris System in 71% of cases but that the discrepancies had no observable impact on the actuarial local control in the short follow-up period (28 +/- 15 months). When we compared, in time sequence, the first 35 patients treated between 1988 and 1989 (Early group) with the last 37 treated between 1990 and 1992 (Later group), we saw that staff members had improved their application of the therapy by more often using the recommended length of active lines. Staff performance in the Later group was still far from ideal, however, as the actual length used differed from the length recommended in 51% of the cases. At present we are insisting on stricter application of the Paris System guidelines for lip brachytherapy. Our study suggests that auditing performance is worthwhile and we recommend that radiotherapists apply this analytical quality assurance method, especially when several new physicians join a department.

Carcinoembryonic antigen in tissue and serum from breast cancer patients relationship with steroid receptors and clinical applications in the prognosis and early diagnosis of relapse.

From July 1982 to August 1994, CEA levels were determined in 298 mammary tissue samples (30 benign, 242 primary breast cancer and 26 metastatic breast cancer). CEA serum levels were also evaluated in 30 patients with benign diseases, 153 patients with primary breast cancer and 26 patients with metastases. CEA tissue levels in both pellet and cytosol were significantly higher in samples from cancerous than from non malignant tissues (p < 0.0001), and higher in the pellet than in the cytosol (p < 0.0001). CEA in the pellet and cytosol were related to steroid receptors, with the highest levels being observed in ER+/PR+ tumors (p < 0.001). They were, however, not related to other pathological parameters such as tumor size or nodes. There was a correlation between CEA pellet and CEA serum in both patients with primary or metastatic tumors, with significantly higher CEA serum levels in patients with CEA pellet positivity than in those with CEA pellet negativity. CEA serum levels were a prognostic factor (DFS and OS) in the whole group as well as in node-positive and node-negative breast cancer patients. This prognostic value was only found in patients with CEA pellet positivity. In the follow-up of 143 NED patients, abnormal CEA serum levels rose prior to the diagnosis of relapse in 73% (29/40) of CEA pellet+ patients with distant recurrences but in only 9% (2/22) of CEA pellet- cases (p < 0.0001). In summary, CEA evaluation in tissue improves the CEA clinical application, selecting those patients whose serum CEA will be useful in the prognosis and early diagnosis of recurrence.

Prospective evaluation of CEA and CA 15.3 in patients with locoregional breast cancer.

The tumor markers, CEA and CA 15.3, were prospectively studied in the sera of 1057 untreated patients with locoregional breast cancer diagnosed from 1983 to 2001. Abnormal CEA and CA 15.3 serum levels were found in 13% and 18.8% of the patients, respectively. One tumor marker or another was abnormal in 22.8% of the patients. Both tumor markers were correlated with tumor size and nodal involvement, with significantly higher concentrations in patients with larger tumors or in patients with nodal involvement. CEA was also related to the histological type and CA 15.3 with the histological grade. Univariate prognostic evaluation showed that tumor size, nodal involvement, histological grade, steroid receptors, adjuvant treatment, CEA, CA 15.3 and treatment before surgery were prognostic factors in both disease-free survival (DFS) and overall survival (OS). Similar results were obtained in node-positive patients, with the same factors being prognostic, excluding adjuvant treatment and CA 15.3, in both DFS and OS. Multivariate analysis showed that tumor size, nodal involvement, histological grade, ER and CEA were independent prognostic factors in both DFS and OS in the whole group as well as in node-positive patients. In contrast, tumor size was the only useful parameter in the prognosis of node-negative patients. CA 15.3 was useful for prognosis (OS) in node-negative patients. In summary, tumor markers are useful tools in the prognostic evaluation of patients with breast cancer.

Prospective evaluation of tumor markers (c-erbB-2 oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer.

Tumor markers were prospectively (CEA and CA 15.3) or retrospectively (c-erbB-2) studied in the sera of 503 untreated patients with breast cancer diagnosed from 1988 to 2001. Abnormal c-erbB-2 levels (> 15 U/ml) were found in 7%, CEA in 12% and CA 15.3 in 13% of the 503 patients. C-erbB-2 serum levels were only related to c-erbB-2 in tissue, with significantly higher concentrations in patients with positivity in tissue. All the tumor markers (c-erbB-2 only in patients with positivity in tissue) were correlated with tumor size, TNM and nodal involvement. CEA was also related to menopausal status, c-erbB-2 overexpression in tissue and ER. Univariate analysis (mean follow-up 8 years) showed that CEA and CA 15.3 were prognostic factors with significantly shorter disease-free survival (DFS) and overall survival (OS) in patients with pretreatment tumor marker positivity. Multivariate analysis in DFS and in OS showed that nodal involvement CEA and ER but not tumor size, menopausal status, histological grade, histology, CA 15.3, c-erbB-2, PgR, adjuvant treatment, p53 (345 patients) or c-erbB-2 in tissue are independent prognostic factors. In summary, tumor markers are a useful, inexpensive and reproducible tool for prognosis in breast cancer.

C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients.

UNLABELLED: C-erbB-2, CEA and CA 15.3 serial serum determinations were performed in 250 patients (follow-up: 1-4 years, mean 2.5 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Ninety-five patients developed metastases during follow-up. RESULTS: Abnormal c-erbB-2, CEA and CA 15.3 serum levels (> 20 U/ml, > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis were found in 28.4%, 31.6% and 46.3% of the 95 patients with recurrence, with a lead time of 4.2 +/- 2.4, 5.0 +/- 2.5 and 4.6 +/- 2.7 months, respectively. One of the tumor markers was the first sign of recurrence in 69.5% of the patients. Tumor marker specificity was 100% with levels lower than the cut-point in all 155 patients without recurrence. Tumor marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver or bone metastases. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (10/12, 83.3%) than in those without overexpression (1/34, 2.9%) (p = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PgR+ patients (CA 15.3) or in PgR- patients (C-erbB-2) (p < 0.015). In conclusion, tumor markers are useful tools for the early diagnosis of metastases, being the first sign of recurrence in 69.5% of patients with relapse (76.3% in patients with metastases).

C-erbB-2 oncoprotein in the sera and tissue of patients with breast cancer. Utility in prognosis.

C-erbB-2 serum levels were studied in the sera of 50 healthy subjects, 56 patients with benign breast diseases and 412 patients with breast cancer. Using 15 U/ml as the cut-off, no healthy subjects, patients with benign disease and only 2.4% of patients with no-evidence of disease had serum levels higher than this cut-off point. Abnormal c-erbB-2 levels were found in 9.2% of the patients with locoregional breast carcinoma and in 45.4% of those with advanced disease. C-erbB-2 serum levels in patients with locoregional breast cancer were not related to tumor size or nodal involvement. By contrast, significantly higher c-erbB-2 serum levels were found in ER- or PgR- tumors than in those ER+ or PgR+ tumors, in both locoregional or metastatic tumors. The correlation between serum and tissue levels of C-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). In patients with C-erbB-2 overexpression in tissue, c-erbB-2 serum levels were related to tumor size and nodes, with higher values in tumors greater than 5 cm or in those with more than 3 nodes involved. When the prognostic value of this oncoprotein was evaluated, patients with abnormally high presurgical c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative and node-positive patients. Serum concentrations in patients with advanced disease, were related to the site of recurrence with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum level seem to be a useful tumor marker in the prognosis of patients with breast cancer.

Radiotherapy in the maxillary hemangioma.

We present the case of a large maxillary hemangioma treated by radiotherapy. Only 4 cases managed by radiotherapy have been reported in the literature, and most authors negate the radiosensitivity of the tumor. In our patient, the outcome was excellent; by 6 months tumor reduction was more than 50%. This is the first case referred to in the literature whose radiotherapy response was evaluated by magnetic resonance imaging. We describe the clinical and imaging findings of this very rare tumor and its evolution. We also comment on the literature reviewed.

A CT-based simulation for head and neck tumors in centers without CT-simulator and 3D-planning system.

We present a special CT-based simulation technique to optimize the radiotherapy treatments in head and neck tumors. On an immobilization device, some CT hyperdense markers are placed. Real-size CT slices are performed every 5 mm with the patient in the treatment position with the immobilization system. This study permits a more accurate knowledge of the gross tumoral volume and an optimization of the planning treatment.

Simulation by a diagnostic CT for the early vocal cord carcinoma.

The CT-based simulation with a 3D planning system permits the optimization of radiotherapy treatments. The goal is to obtain an increase in the local control and survival with a reduction of the treatment related toxicity. In our hospital, we do not have a CT simulator and our 3D planning system is not yet working, therefore, we have developed a system to simulate radiotherapy treatments using a diagnostic CT. We began by simulating an early vocal cord carcinoma. The rules of this simulation are presented using a clinical case as an example.

[Brachytherapy in the treatment of prostatic carcinoma]. / La braquiterapia en el tratamiento del carcinoma prostático.

Radiotheraphy of prostatic cancer began using brachitherapy. In 1910 Paschkis and in 1911 Pasteau reported treatment of prostatic carcinoma with radium needles. In 1952, Flocks began implanting a colloidaly radioactive gold-198 solution into the prostate after surgical exploration. This approach was optimized by Carlton in 1965 using solid gold-198 implants combined with external beam therapy. In 1972 Withmore et al reported the use of iodine-125 seeds for interstitial irradiation. In 1977 Court and Chassagne introduced after loading techniques using iridium-192. This technique has been developed further by Syed et al. In these settings interstitial radiotherapy is used as localized boost in combination with external beam therapy. Prostate brachytherapy can be divided into temporary implantation using high activity sources, or permanent brachytherapy using the interstitial implantation of iodine-125 or palladium-103 sources. We reported an overview.

Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation

Purpose The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. Material and methods Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10–12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. Results The median age was 64.5 years (40–90). The median follow-up was 62 months (4–86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6–52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3–4 chronic toxicity was observed. Grade 1–2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. Conclusions IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment (AU)

Clinical axillary recurrence after sentinel node biopsy in breast cancer: a follow-up study of 220 patients.

PURPOSE: The aim of this study was to evaluate the frequency of false-negative (FN) sentinel node procedures in patients with breast cancer and the subsequent clinical outcome in such patients. METHODS: A total of 325 breast cancer patients underwent sentinel lymph node biopsy at our institution between June 1998 and May 2004. A 2-day protocol was used to localise the sentinel node with the injection of 99mTc-nanocolloid. There were two phases in the study: the learning phase (105 patients) and the application phase (220 patients). In the learning phase, a complete lymphadenectomy was always performed. In the application phase, sentinel nodes were studied intraoperatively and lymphadenectomy was performed when considered warranted by the pathological intraoperative results. RESULTS: The median follow-up duration in the 220 patients studied during the application phase was 21.2 months (range 4-45 months). In this phase a total of 427 sentinel nodes were obtained (range 1-5 per patient, median 1.99), with 66 positive sentinel nodes in 56 patients (26%). The lymphadenectomies performed were also positive in 25% of cases (14 patients). We observed a total of two false-negative sentinel lymph node results (3.45%). One of them was found during the surgical excision of non-sentinel nodes, and the other presented as an axillary recurrence 17 months postoperatively (1.72% clinical false-negative rate). The latter patient died 1 year after the first recurrence. CONCLUSION: After a median follow-up of 21.2 months we observed only one clinical recurrence among 220 patients. Our results indicate that adequate local control is achieved by application of the sentinel node protocol.

A new theoretical formula for fractionated radiotherapy based on a saturable cellular repair mechanism.

Recently we have published a new model of survival cellular response to radiation based on the existence of a saturable cellular repair mechanism. In the present paper we extend the predictions of this model of calculating the change in total dose necessary to achieve an equal response in a tissue when the dose per fraction in a radiotherapy fractionation schedule is varied. The model provides a new explanation of the difference between late and early radiation reactions. Results obtained from the model for different tissues and standard fractionation schedules are approximately equal to those obtained by the L.Q. (linear-quadratic) model. The model is compatible with in vitro survival curves that are straight at high doses.