The relationship of histological tumor regression grade (TRG) and two different time intervals to surgery following radiation therapy for locally advanced rectal cancer.

BACKGROUND: The objective of this study was to assess the effect of two different time intervals between radiation therapy and surgery for rectal cancer on the histological tumor regression grade (TRG) in the resected specimen. METHODS: Between 1995 and 2000, patients undergoing preoperative radiation therapy and TME for locally advanced (T3N0 and T3N1) mid and low rectal tumors treated in the VU University Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment (5 x 5 Gy) in the VU University medical center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6-8 weeks in the VU University Medical Center (LI group). All available histological material was reevaluated for TRG and correlated to survival. RESULTS: Sixty-seven patients were included in the present study, 28 in the LI group and 39 in the SI group. Patient gender was comparable for both groups with 21 (75%) male patients in the LI group versus 26 (67%) male patients in the SI group (p = 0.46). A T3N0 preoperative tumor stage was found in 21 (75%) patients in the LI group and in 33 (85%) patients in the SI group (p = 0.36). All tumors were histologically proven adenocarcinoma. Patients in the SI group were significantly older (67 vs. 58 years). In the LI group, a significantly more pronounced histological tumor regression was found. A complete response (TRG1), combined with a near complete histological response (TRG 2), were present in 12 patients in the LI group and in four patients in the SI group (p = 0.002). Radicality of resection was comparable for both groups. With a follow-up of over 60 months, there were no statistically significant differences between the SI and LI groups regarding local control, overall, or disease-free survival. CONCLUSION: Although histological tumor regression is significantly more pronounced following a long interval between radiation therapy and surgery, in the present study, this is not reflected in a better radical resection rate, local control or better overall and disease-free survival.

Imaging-documented repeated intratumoral hemorrhage in vestibular schwannoma: a case report.

Intratumoral hemorrhage in vestibular schwannomas is rare. Symptoms often have an acute onset and include headache, nausea, vomiting, vertigo, and depressed consciousness. Intratumoral hemorrhage is probably caused by vascular fragility associated with tumor characteristics and growth. With hemorrhage in VS being rare, repeated hemorrhage has only been reported twice, and on clinical grounds only. The present report details the case of acute neurological deterioration in a patient with repeated intratumoral hemorrhage inside a vestibular schwannoma with computed tomography and magnetic resonance imaging confirmation. To our knowledge, repeated hemorrhage in vestibular schwannoma with radiological confirmation has not been reported before.

Radiosurgery of brain arteriovenous malformations in children.

OBJECTIVE: The authors describe their experience in treating 22 children with a single brain arteriovenous malformation (bAVM) using a dedicated LINAC stereotactic radiosurgery unit. METHODS: The findings of 22 consecutive patients < or = 18 years of age who underwent radiosurgery for a single bAVM and with at least 24 months of follow-up, or earlier proven obliteration,were reviewed. The median age at radiosurgery was 13.8 years,with a hemorrhagic presentation in 86%. Median bAVM-volume was 1.8 ml, with a median prescribed marginal dose of 19.0 Gy. RESULTS: The crude complete obliteration-rate was 68% (n = 15) after a median follow-up of 24 months. The actuarial obliteration- rate was 45 % after two years and 64 % after three years. Patients with a radiosurgery-based AVM score < or = 1 more frequently had an excellent outcome than patients with a bAVM score > 1 (71% vs. 20%, P = 0.12), as well as an increased obliteration rate (P = 0.03) One patient died from a bAVM-related hemorrhage 27 months after radiosurgery, representing a postradiosurgery hemorrhage rate of 1.3%/year for the complete followup interval. Overall outcome was good to excellent in 68% (n = 15). Radiation-induced changes on MR imaging were seen in 36% (n = 8) after a median interval of 12.5 months, resulting in deterioration of pre-existing neurological symptoms in one patient. CONCLUSIONS: Radiosurgery is a relatively effective, minimally invasive treatment for small bAVMs in children. The rebleeding rate is low, provided that known predilection places for bleeding had been endovascularly eliminated.Our overall results compare unfavourably to recent pediatric microsurgical series, although comparison between series remains imprecise. Nevertheless, when treatment is indicated in a child with a bAVM that is amenable to both microsurgery or radiosurgery, microsurgery should carefully be advocated over radiosurgery, because of its immediate risk reduction.

Ewing's sarcoma and primitive neuroectodermal tumour in adults: single-centre experience in The Netherlands.

BACKGROUND: Ewing's sarcoma and peripheral primitive neuroectodermal tumours (PNET) are rare tumours and closely related. They occur most often in children and adolescents. Few studies have been published on treatment outcome in adult patients. METHODS: We performed a retrospective analysis of patients aged >16 years who were primarily treated at our university hospital for Ewing's sarcoma or PNET. In general, treatment consisted of long-term multiagent chemotherapy, interrupted by individualised local treatment consisting of surgery and/or radiotherapy. We reviewed clinical features and outcomes to present our experience with Ewing's sarcoma and PNET in adults. RESULTS: From 1979 to 2002, 27 patients with Ewing's sarcoma (20) or PNET (7) were treated. There were 22 men and 5 women, with a median age of 25 years (range 17-49). Ten patients presented with metastases predominantly in lungs (4) or bones (6). Combination therapy consisted of chemotherapy (27), surgery (16) and radiotherapy (16). After a median follow-up of ten years, 14 patients have died (toxicity = 2, progressive disease = 12) and 13 patients are alive and free of disease. Five-year overall survival was 58%. All four patients with bone metastases died, while all five patients presenting with lung metastases are disease-free. CONCLUSION: The five-year overall survival of 58% in this small series on adult patients is in line with paediatric study outcomes. Patients with lung metastases may even be cured by multimodality therapy. We therefore strongly advocate referral of patients with this rare disease to a specialised oncology centre.

Treatment of primary cutaneous B-cell lymphomas of follicle center cell origin: a clinical follow-up study of 55 patients treated with radiotherapy or polychemotherapy.

PURPOSE: Primary cutaneous follicle center cell lymphomas (PCFCCL) are a distinct group of cutaneous B-cell lymphomas with a favorable prognosis after radiotherapy (RT) or polychemotherapy (PCT). In the literature, conflicting data exist regarding the efficacy and the relapse rate of both treatment modalities. In the present study, treatment results and follow-up data of a large group of PCFCCL are evaluated. PATIENTS AND METHODS: Fifty-five patients with a PCFCCL who presented with skin lesions on either the head (n = 12), the trunk (n = 35), or lower legs (n = 8), and who were initially treated with RT (40 cases) or PCT (15 cases) were studied. RESULTS: RT resulted in a complete remission in all 40 cases. Eight cases relapsed and three of these patients died as a result of their lymphoma. The estimated 5-year survival was 89%. Four of eight relapses and all three lymphoma-related deaths occurred in the group of patients presenting with tumor(s) on the lower legs. Treatment with cyclophosphamide, doxorubicin vincristine, and prednisone (CHOP) or cyclophosphomide, vincristine, and prednisone (COP) resulted in a complete remission in 14 of 15 cases. All four cases treated with COP relapsed, whereas only two of 11 patients treated with CHOP had a relapse. The estimated 5-year survival rate of the PCT group was 93%. CONCLUSION: Both RT and CHOP PCT are highly effective modes of treatment for PCFCCL. In localized PCFCCL, RT is the treatment of choice. In patients with multiple tumors involving anatomic nonrelated parts of the skin, CHOP rather than COP PCT is the preferred mode of treatment. PCFCCL on the lower legs, a subgroup that characteristically occur in elderly patients, have a higher relapse rate and a less favorable prognosis than PCFCCL presenting on the head or trunk.

Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer.

A feasibility study was performed to assess the toxicity and efficacy of a combination of gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable LAPC were included; the median age of the patients was 63 years (range 39-74 years). The performance status ranged from 0 to 2. Gemcitabine was administered at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy, on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the response and toxicity. All patients were evaluable for toxicity and response. The objective response rate was 29.2% (1 complete remission+6 partial remissions); 12 patients had stable disease. However, 2 of the radiological partial remissions were shown to be complete remissions by pathology assessment. Median duration of response was 3 months (range 1-35+months). Median time to progression was 7 months (range 2-37+months). Median survival was 10 months (range 3-37+months). Dose reduction or omission of gemcitabine was necessary in 10 patients. Non-haematological toxicity consisted of 87.5% nausea and vomiting grade I-II, diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months after treatment. Anaemia grade III-IV was observed in 8.3% of the patients. Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in 16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour cells were found. In addition, in the patient who suddenly died of a fistula between the duodenum and aorta, no viable tumour cells were detectable at autopsy. Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination.

Proliferation and clonal survival of human lung cancer cells treated with fractionated irradiation in combination with paclitaxel.

PURPOSE: This study was performed to determine the effects of a continuous exposure to paclitaxel (taxol) in combination with fractionated irradiation on cell proliferation and survival. METHODS AND MATERIALS: Human lung carcinoma cells (SW1573) were given a daily treatment with 3 Gy of x-rays during 5 days in the continuous presence of 5 nM taxol. The surviving fraction and the total number of cells were determined every 24 h before and immediately after irradiation. RESULTS: Irradiation with 5 x 3 Gy and 5 nM taxol cause approximately the same inhibition of cell proliferation. In combination these treatments have an additional effect and the cell population increases no further after the first 24 h. Whereas the cells become more resistant to taxol after the first 24 h with a minimum survival of 42%, taxol progressively reduces the population of surviving cells in combination with x-rays when the number of fractions increases, up to 25-fold relative to irradiation alone. The enhancement effect of 5 nM taxol is likely to be attributed to an inhibition of the repopulation during fractionated irradiation and not to an increased radiosensitivity. Only after treatment with 10 or 100 nM taxol for 24 h, which is attended with a high cytotoxicity, is moderate radiosensitization observed. CONCLUSION: Taxol, continuously present at a low concentration with little cytotoxicity, causes a progressive reduction of the surviving cell population in combination with fractionated irradiation, mainly by an inhibition of the repopulation of surviving cells between the dose fractions.

Single-fraction vs. fractionated linac-based stereotactic radiosurgery for vestibular schwannoma: a single-institution study.

PURPOSE: In this single-institution trial, we investigated whether fractionated stereotactic radiation therapy is superior to single-fraction linac-based radiosurgery with respect to treatment-related toxicity and local control in patients with vestibular schwannoma. METHODS AND MATERIALS: All 129 vestibular schwannoma patients treated between 1992 and June 2000 at our linac-based radiosurgery facility were analyzed with respect to treatment schedule. Dentate patients were prospectively selected for a fractionated schedule of 5 x 4 Gy and later on 5 x 5 Gy at the 80% isodose in 1 week with a relocatable stereotactic frame. Edentate patients were prospectively selected for a nonfractionated treatment of 1 x 10 Gy and later on 1 x 12.5 Gy at 80% isodose with an invasive stereotactic frame. Both MRI and CT scans were made in all 129 patients within 1 week before treatment. All patients were followed yearly with MRI and physical examination. RESULTS: A fractionated schedule was given to 80 patients and a single fraction to 49 patients. Mean follow-up time was 33 months (range: 12-107 months). There was no statistically significant difference between the single-fraction group and the fractionated group with respect to mean tumor diameter (2.6 vs. 2.5 cm) or mean follow-up time (both 33 months). Only mean age (63 years vs. 49 years) was statistically significantly different (p = 0.001). Outcome differences between the single-fraction treatment group and the fractionated treatment group with respect to 5-year local control probability (100% vs. 94%), 5-year facial nerve preservation probability (93% vs. 97%), and 5-year hearing preservation probability (75% vs. 61%) were not statistically significant. The difference in 5-year trigeminal nerve preservation (92% vs. 98%) reached statistical significance (p = 0.048). CONCLUSION: Linac-based single-fraction radiosurgery seems to be as good as linac-based fractionated stereotactic radiation therapy in vestibular schwannoma patients, except for a small difference in trigeminal nerve preservation rate in favor of a fractionated schedule.

Fractionated stereotactic radiation therapy and single high-dose radiosurgery for acoustic neuroma: early results of a prospective clinical study.

PURPOSE: To prospectively assess the local control and toxicity rate in acoustic neuroma patients treated with linear accelerator-based radiosurgery and fractionated stereotactic radiation therapy. METHODS AND MATERIALS: We evaluated 37 consecutive patients treated with stereotactic radiation therapy for acoustic neuroma. All patients had progressive tumors, progressive symptoms, or both. Mean tumor diameter was 2.3 cm (range 0.8-3.3) on magnetic resonance (MR) scan. Dentate patients were given a dose of 5x4 Gy or 5x5 Gy and edentate patients were given a dose of 1x10 Gy or 1x12.50 Gy prescribed to the 80% isodose. All patients were treated with a single isocenter. RESULTS: With a mean follow-up period of 25 months (range 12-61), the actuarial local control rate at 5 years was 91% (only 1 patient failed). The actuarial rate of hearing preservation at 5 years was 66% in previously-hearing patients. The actuarial rate of freedom from trigeminal nerve toxicity was 97% at 5 years. No patient developed facial nerve toxicity or other complications. CONCLUSION: In this unselected series, fractionated stereotactic radiation therapy and linear accelerator-based radiosurgery give excellent local control in acoustic neuroma. It combines a high rate of preservation of hearing with a very low rate of other toxicity, although follow-up is relatively short.

Effect of CT-based treatment planning on portal field size and outcome in radiation treatment of localized prostate cancer.

The portal field sizes of 361 consecutive patients treated with curative radiotherapy for localized prostate cancer were measured. The introduction of CT-based information resulted in a significant increase of field sizes, leading to an almost doubling of the treated volume, some increase in late rectal toxicity, but also in local control.

Efficacy of a synthetic mesh sling in keeping the small bowel in the upper abdomen to prevent radiation enteropathy in gynecologic malignancies.

Radiation therapy in gynecological malignancies is limited by the frequent occurrence of radiation enteropathy at effective dose levels of 45 Gy and higher. Elevation of the small bowel out of the true pelvis should enable doses of up to 60-70 Gy to be given without damaging the small bowel. We report a feasibility study concerning elevation of the small bowel out of the true pelvis, by creating an intra-abdominal sling with a synthetic mesh. Twelve patients with pelvic gynecological malignancies were included since 1986. In all patients peroperative application of the mesh was possible. In ten patients adequate elevation of the small bowel was achieved. Two patients showed a right-sided herniation of a small bowel loop on a control barium opacification, performed 1 week postoperatively. In one of these a fistula occurred after resecuring the mesh. The most important problem in this study, as has also been reported elsewhere, was a herniation of a small bowel loop. The incidence is probably inversely correlated with the skill of the surgeon and will therefore be reduced with increasing experience. Future long-term studies should address the issue whether or not radiation enteropathy can be prevented by this method.

[Primary high-dose chemotherapy with hematopoietic growth factors followed by surgery and radiotherapy in stage III breast carcinoma; a Phase II study in 15 patients]. / Primaire hoog gedoseerde chemotherapie met hematopoëtische groeifactoren gevolgd door chirurgie en radiotherapie bij stadium III-mammacarcinoom; een fase II-onderzoek bij 15 patiënten.

OBJECTIVE: To establish if the prognosis of a stage III breast carcinoma is improved by primary high-dose chemotherapy in combination with haemopoietic growth factors, followed by radical surgery and radiotherapy. DESIGN: Phase II study. SETTING: University Hospital Free University, Amsterdam. METHOD: Fifteen patients with a locally advanced breast carcinoma (stages IIIA or IIIB) were treated every three weeks with doxorubicin 90 mg/sq.m. and cyclophosphamide 1000 mg/sq.m., followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 250 micrograms/sq.m. from day 2 up to and including day 12. After 4-6 of these courses the treatment in principle was continued with a modified radical mastectomy, followed by radiotherapy. Median duration of follow-up was 18 months. RESULTS: All tumours were reduced by over 50%. 10/15 Patients went into clinical complete remission; in 6/9 of these, pathological examination revealed only microscopical tumour rests, in the other three the rest diameter was < or = 1 cm. The haematological toxicity was mild. Grade III-IV bone marrow suppression was followed by rapid return to normal of the numbers of neutrophil granulocytes and thrombocytes under the influence of GM-CSF. The non-haematological toxicity manifested itself with nausea and vomiting, stomatitis and mild side effects attributable to GM-CSF. CONCLUSION: It appears justified in the treatment of locally advanced breast carcinoma to start with chemotherapy. Dose escalation of efficacious chemotherapeutics resulted in a large number of complete remissions.

[Stereotaxic irradiation of vestibular schwannoma (acoustic neuroma)]. / Stereotactische bestraling van het vestibulair schwannoom (acusticusneurinoom).

A vestibular schwannoma (acoustic neurinoma) is a benign tumour localized in the cerebellopontine angle; it can give rise to cranial nerve symptoms. In recent years stereotactic irradiation has become an alternative to radical surgery. Stereotactic irradiation is administered with a gamma knife unit or with an adapted linear accelerator, as a single fraction (radiosurgery) or fractionated (stereotactic radiation therapy). Stereotactic irradiation gives local control rates of over 90%. Post treatment hearing preservation rate is over 60% and treatment related toxicity is low. Comparable treatment results are also found in the Netherlands at the VU-Ziekenhuis in Amsterdam.

[Stereotactic radiosurgery with adjusted linear accelerator for cerebral arteriovenous malformations: preliminary results in the Netherlands]. / Stereotactische radiochirurgie met aangepaste lineaire versneller voor cerebrale arterioveneuze malformaties: eerste ervaringen in Nederland.

OBJECTIVE: To assess the effects of stereotactic radiosurgery of a cerebral arteriovenous malformation (AVM). DESIGN: Prospective. METHOD: In November 1991-December 1995 linear acceleration radiosurgery was performed on 29 patients for their 30 cerebral AVMs in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands. There were 15 females and 14 males with a mean age of 37.1 years (range: 13-58). Generally one isocentre was used and 15 Gy was given to the margins of the AVM at the 80% isodose. The mean target volume was 2.4 ml (range; 0.5-8.2). After 6 months, one year and thereafter every year, neurological and MRI-controls took place, in the outpatient ward. Angiography was performed after an average of 35 months (range: 24-70) to check if the AVM had obliterated. RESULTS: Angiographic post-treatment results were available in 27 patients and MRI information in one. Angiographic obliteration occurred in 20 patients (71%). No permanent radiation-induced neurological deficit was seen, nor did any hemorrhage occur during the interval between irradiation and obliteration.

Tumor-volume changes after radiosurgery for vestibular schwannoma: implications for follow-up MR imaging protocol.

BACKGROUND AND PURPOSE: The outcome of radiosurgery for vestibular schwannoma (VS) is assessed by posttreatment measurement of tumor size and could be influenced by the timing and quality of the assessment. This study evaluates the volumetric changes of VS after radiosurgery and proposes a radiologic follow-up program. MATERIALS AND METHODS: Of 142 patients with VS treated with radiosurgery, we selected patients who were followed at least 3 times during a minimum of 32 months with a T1-weighted gadolinium-enhanced high-resolution 3D MR imaging examination identical to the pretreatment MR imaging. Forty-five patients were identified with a mean follow-up of 50 months (range, 32-78 months). Pre- and posttreatment tumor volumes were calculated by using BrainSCAN software by manually contouring tumors on each MR imaging study. Volume changes of >13% were defined as events. RESULTS: At last follow-up MR imaging, volumes were smaller in 37 (82.2%) of the 45 patients. Eleven (29.7%) of these 37 tumors showed transient swelling preceding regression, with a median time to regression of 34 months (range, 20-55 months). Seven (15.6%) of the 45 tumors had volume progression compared with the tumor on pretreatment MR imaging studies. Of these 7 tumors, 3, however, had volume regression compared with the preceding MR imaging study, and in 4, volume progression was ongoing. One tumor remained the same. CONCLUSIONS: Tumor-volume measurements by standardized T1-weighted gadolinium-enhanced high-resolution 3D MR imaging follow-up protocols revealed good local control of VS after radiosurgery. The first-follow-up MR imaging at 2 years and the second at 5 years postradiosurgery differentiated transient progression from ongoing progression and may prevent unnecessary therapeutic interventions.

Preoperative radiation therapy for locally advanced rectal cancer: a comparison between two different time intervals to surgery.

BACKGROUND: Although it is now considered a standard treatment to irradiate an advanced mid or low rectal tumor before surgical total mesorectal excision (TME), the optimal time interval between radiation therapy and surgery remains controversial. MATERIALS AND METHODS: Between 1995 and 2005, patients undergoing preoperative radiation therapy and TME for locally advanced mid and low rectal tumors treated in the VU Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment in the VU Medical Center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6-8 weeks in the VU Medical Center (LI group). Preoperative tumor staging, operative data, postoperative complications, pathology results, and follow-up were compared. RESULTS: The SI group (N=57) underwent surgery after a median delay of 4 days and the LI group (N=51) after 45 days. Operative data and short-term morbidity were comparable for both groups. However, significantly higher numbers of complete remissions (12 vs 0%), tumor downstaging (55 vs 26%), and less lymph-node metastases (22 vs 44%) were found in the LI group. No significant differences were found regarding local control or long-term survival after a median follow-up of 34 months. CONCLUSION: Several advantages, such as complete remissions and downstaging in the LI group, do not appear to have expression in a better survival or less local recurrences after a median follow-up of 34 months. Although larger (randomized) studies will be needed for definite conclusions, this may indicate that patients can be operated on within 2 weeks after radiation therapy.

Hypofractionated radiation therapy in unresectable stage III non-small cell lung cancer.

BACKGROUND: Hypofractionation is the current choice for radiation therapy for patients with unresectable non-small cell lung cancer (NSCLC) at the authors' institute. METHODS: In this nonrandomized study, three hypofractionated radiation schedules (40-Gy split course; 30-32 Gy in 6 fractions and 24 Gy in 3 fractions) are evaluated in 301 patients with unresectable Stage III NSCLC: RESULTS: Patients with Stage IIIA disease treated with a 40-Gy split course had longer survival (P < 0.005) and a lower local relapse rate (P < 0.01), but a higher distant failure rate (P < 0.01) than those receiving 24-32 Gy. Survival for patients with Stage IIIA disease treated with 40 Gy at 1, 2, and 5 years was 47%, 22%, and 7%, respectively. For patients with Stage IIIB disease, the radiation scheme used did not correlate with survival and relapse rates. Survival at 1, 2, and 5 years was 30%, 9%, and 2%, respectively. The hypofractionated radiation schemes were well tolerated, and no severe complications were recorded. CONCLUSIONS: In patients with Stage IIIA disease, 40-Gy split-course radiation therapy yields survival rates comparable to those achieved with conventional radiation therapy. In patients with Stages IIIB and IV NSCLC, 24 Gy in 3 weekly fractions yields survival rates comparable to those achieved with higher total doses given in more fractions.