Salvage Radiotherapy After High-Intensity Focussed Ultrasound for Recurrent Localised Prostate Cancer

Background

Radiotherapy is a treatment option in the case of local failure following treatment for localised prostate cancer with high-intensity focussed ultrasound (HIFU).

Objective

Our aim was to evaluate tolerance and oncologic control with salvage radiotherapy (SRT) after HIFU failure and to identify predictive factors of success.

Design, setting, and participants

From March 1995 to March 2008, all patients who presented with histologically proven persistent local disease following HIFU and were treated with curative intent SRT (with or without hormonal treatment) were included in this single-centre retrospective study.

Intervention

Patients underwent conformal radiotherapy. The median dose of conformal treatment was 72 Gy (65–78 Gy).

Measurements

The primary outcome measure was progression-free survival (PFS) defined as no biochemical relapse (three consecutive rises in prostate-specific antigen [PSA] with a velocity >0.4 ng/ml per year or PSA >1.5 ng/ml) and no additional treatment. Predictive factors of failure were examined in univariate and multivariate analyses. Adverse events in terms of urinary and digestive toxicity, urine incontinence, and erectile dysfunction (ED) were reported.

Results and limitations

The median (range) and mean (standard deviation) follow-up of the 100 patients analysed was 33 mo (5–164 mo) and 37.2 mo (23.6 mo), respectively. Eighty-three patients received SRT alone, and 17 received SRT and androgen-deprivation therapy. For the 83 patients treated with exclusive radiation therapy, PFS was 72.5% at 5 yr and 93%, 67%, and 55% for the low-, intermediate-, and high-risk groups, respectively. In the univariate analysis, PSA level prior to SRT, risk status, PSA nadir after SRT, PSA nadir after SRT >0.2 ng/ml, and time to achieve this nadir were all predictive of failure. In the multivariate analysis, PSA nadir post-SRT with a threshold at 0.2 ng/ml and time to achieve this nadir were the significant predictive factors of failure. Gastrointestinal toxicity was low; urinary toxicity grade ≤2 was 34.5%. Four were grade 3 (4.7%), one was grade 4 (1.2%), and one was grade 5 (1.2%). The incidence of severe ED (International Index of Erectile Dysfunction–5 score 5–10) was 14% pre-HIFU, and 51.9% and 82.3% pre- and post-SRT, respectively. Because our study was retrospective, results have to be interpreted cautiously.

Conclusions

SRT provides satisfactory oncologic control after HIFU failure with little (or mild) additional toxicity. These results warrant further investigation.     

Stereotactic Radiotherapy for Cushing's Disease and Prolactinoma

Stereotactic radiotherapy (SRT) for secretory pituitary adenoma offers precise localization of dose with potential sparing of optic and hypothalamic functions. We collated the indications, treatment parameters, and both the clinical and biochemical results of Stereotactic radiotherapy for ACTH- 1 and prolactin-secreting pituitary adenoma. Between May 1990 and February 1996, nine patients (4 males and 5 females) with a mean age of 31.9 years had fractionated SRT for ACTH- or prolactin-secreting pituitary adenomas (Cushing's disease: n = 5; prolactinoma: n = 3; Nelson's syndrome: n = 1). These 9 patients had subtotal transphenoidal resections before SRT. An additional patient with Cushing's disease had aborted transphenoidal surgery and single-fraction Stereotactic radiosurgery (SRS). Prior to SRT, 4 patients received planned conventional fractionated external beam radiotherapy (XRT) (median dose 33.3 Gy). The median SRT dose was 34.5 Gy (range 14.4–50.4 Gy). The median total radiation dose (XRT plus SRT) for patients receiving fractionated treatment was 47.7 Gy. The median follow-up was 62 months (range 22–91 months). One patient with Nelson's syndrome was lost to follow-up. Of the 9 evaluable patients, none required reoperation for growth of pituitary tumor and all had radiographic control as shown by serial MRI scans. In 4 of the 6 patients with Cushing's disease, treatment resulted in normalization of hormone levels and resolution of symptoms. All 4 patients were able to discontinue medications. In 2 patients, normalization occurred within 4 months of treatment. Two patients with Cushing's disease failed, requiring adrenalectomy. For patients with prolactinoma, treatments resulted in a significant decrease of plasma prolactin levels. All patients treated for prolactinoma became asymptomatic; 2 were able to discontinue bromocriptine and 1 patient had a successful pregnancy. After radiation therapy, 1 patient developed new hypopituitarism. None of the patients developed worsened visual acuity, visual fields, or new neurological deficits. SRT with or without XRT may yield meaningful reductions in hormone levels with concomitant clinical improvement in selected patients with prolactinomas or Cushing's disease. In certain situations, combining conventional XRT with SRT is appropriate. Modifications of the Stereotactic radiation delivery may maximally reduce the hypothalamic dose, thereby possibly reducing the risk of clinical hypopituitarism. This treatment is safe and is without visual or other neurological toxicity.     

Toxicity following high-dose salvage radiotherapy after radical prostatectomy

OBJECTIVE: To assess gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated with salvage radiotherapy (SRT) at doses of 70.2 Gy after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: Medical records were reviewed retrospectively to identify patients treated with SRT after RRP between January 1999 and December 2005. Of the 62 patients identified, 30 were included for analysis. GI and GU toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and the American Urological Association Symptom Index (AUASI), respectively. RESULTS: The median AUASI score of the 17 patients with scores before SRT was 4, of the 24 with scores after SRT was 6, and of the 15 with scores before and after SRT the median increase was 3. Of the 29 patients with GI toxicity data, nine (31%) had diarrhoea after SRT (three after <70.2 Gy and six after 70.2 Gy). In all cases, the diarrhoea was mild (grade 1). Of all patients, 12 (41%) had proctitis after SRT (four after <70.2 Gy and eight after 70.2 Gy); the proctitis was grade 1 in four and grade 2 in eight, with no cases of grade 3 proctitis. There was no statistically significant difference in the median change in AUASI scores and GI toxicity incidence between patients receiving <70.2 or 70.2 Gy of SRT. CONCLUSION: High-dose SRT (70.2 Gy) is generally well tolerated with acceptable low-grade GI toxicity and minimal changes in AUASI scores.     

Hypofractionated Stereotactic Radiotherapy for Recurrent Malignant Gliomas

Objective: The results of hypofractionated stereotactic radiotherapy (SRT) for the treatment of unselected patients with malignant glioma recurrent after conventional therapy were analyzed. Materials and Methods: Between January 1997 and March 1999, 21 patients with recurrent malignant glioma received SRT at UCLA. All patients received prior conventional radiotherapy (median 6000 cGy). The interval from initial diagnosis to SRT varied from 3 to 99 months (median 11). Tumor volume ranged from 4.5 to 33.7 cc (median 12). Fifteen patients had glioblastoma multiforme and 3 had anaplastic astrocytoma with an oligodendroglial component. Two patients with prior low-grade astrocytoma and one with an unbiopsied brainstem tumor did not have pathological confirmation of tumor grade at time of relapse. Five patients had multifocal recurrences and 11 had imaging evidence of indistinct tumor. Twelve patients had progressive disease after receiving salvage chemotherapy. Patients received 4–6 daily fractions of 400 to 600 cGy. Median total SRT dose was 2500 cGy. Follow-up ranged from 1 to 20 months and no patients were lost. Results: The actuarial median and one-year survival were 6.7 months and 15%, respectively. Fifteen patients died of progressive glioma and one of a pulmonary embolus. Sixteen patients relapsed after SRT: 11 local, 4 local plus distant, one marginal. All patients with distant relapse also had local failure at some time. The median time to local relapse for the 14 patients with an initial component of local failure was 5 months. There were trends to superior survival for those with an initial diagnosis of nonglioblastoma and those with frontal/occipital lobe recurrences. No patient developed documented radionecrosis. Two patients underwent operation following SRT. Histopathological analysis of the operative specimen revealed malignant glioma. Conclusions: The authors conclude that hypofractionated SRT is a feasible, safe alternative for patients with recurrent malignant glioma. Local failure represents the overwhelming pattern of relapse after SRT, regardless of the clinical or imaging characteristics of patients with recurrent tumor. Improving the outcome for this group of patients may require a multimodality approach of SRT plus concurrent chemotherapy.     

Validation of a nomogram to predict disease progression following salvage radiotherapy after radical prostatectomy: results from the SEARCH database

OBJECTIVE

To externally validate the nomogram published by Stephenson et al. (termed the ‘Stephenson nomogram’) to predict disease progression after salvage radiotherapy (SRT) among patients with prostate cancer from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

PATIENTS AND METHODS

We analysed data from 102 men treated with SRT for prostate‐specific antigen (PSA) failure after prostatectomy, of whom 30 (29%) developed disease progression after SRT during a median follow‐up of 50 months. The predicted 6‐year progression‐free survival (PFS) was compared to the actuarial PFS using calibration plots. The accuracy of the nomogram to risk‐stratify men for progression was assessed by the concordance index.

RESULTS

The median PSA and PSA doubling time before SRT was 0.6 ng/mL and 10.3 months, respectively. The 6‐year actuarial disease‐free progression after SRT was 57% (95% confidence interval 42–69%). The overall concordance index of the Stephenson nomogram was 0.65. The nomogram predicted failure more accurately at the extremes of risk (lowest and highest) but in intermediate groups, the accuracy was less precise. Of the 11 variables used in the nomogram, only negative margins and high PSA level before SRT were significantly associated with increased disease progression.

CONCLUSION

The Stephenson nomogram is an important tool to predict disease progression after SRT following radical prostatectomy. It adequately predicted progression in SEARCH with reasonable accuracy. Also, in SEARCH, disease progression was predicted by similar disease characteristics. However, the overall modest performance of the model in our validation cohort indicates there is still room for improvement in predictive models for disease progression after SRT.     

Once‐weekly hypofractionated radiotherapy for breast cancer: First results of a phase II clinical trial

Hypofractionated radiotherapy (HF) in 15 or 16 daily fractions is well established as an alternative in early breast cancer after breast‐conserving surgery. Evidences for a whole‐breast treatment even shorter, in 5‐10 fractions, are still scarce. Women 50 years or older, with early breast tumor (pT1‐2pN0), after breast‐conserving surgery were eligible to enter in this phase II trial and received whole breast once‐weekly hypofractionated radiotherapy (wHF‐RT) to a total dose of 30 Gy, in 5 fractions of 6 Gy. During treatment and in post‐treatment follow‐up the toxicity was assessed and graduated according to the “Common Terminology Criteria for Adverse Events” (CTCAE), v3.0. Breast pictures for esthetic comparison were taken in 5 timepoints and 2 breast surgeons independently graduated the cosmetics changes. The trial was registered with ClinicalTrials.gov, number NCT01965483. From October 2013 to November 2015, 44 patients were enrolled in the trial and treated according to the protocol of wHF‐RT. The median age was 70.5 years (51‐88 years), and the median follow‐up was 22 months (9‐33 months). Skin erythema was the most common acute adverse event. At the end of radiation, 30 patients (68.2%) had any grade of radiation dermatitis. Concerning cosmetic appearance, there was no significant difference between pretreatment and 1 year assessments. The 2‐year overall survival and disease‐free survival were, respectively 96.8% and 97.7%. There was only one distant recurrence and no local or regional recurrence. Once‐weekly hypofractionated radiotherapy is a feasible and well tolerated alternative for early breast cancer adjuvant management with acceptable acute toxicity and esthetic outcomes.     

Paragangliomas of the temporal bone: results of different treatment modalities in 53 patients

Summary.  Background: The authors retrospectively compared the results of three different treatment modalities (surgery, conventional radiotherapy and gamma knife radiosurgery) in patients with paragangliomas of the temporal bone, in order to determine the optimal current treatment concept.  Method: Between 1978 and August 2001, 53 patients (12 men and 41 women; mean age, 58.3 years; range, 17 to 84 years) with paragangliomas of the temporal bone were treated at the neurosurgery and ENT departments of the University of Vienna. According to the Fisch classification, 6 patients had class B tumours, 20 had class C, and 27 patients had class D tumours. Thirty-two patients (mean age, 57.0 years; 6 B, 14 C, 12 D) underwent surgery. In 17 cases the tumour was embolised prior to surgery. Nine patients (mean age, 73.9 years; 6 C, 3 D) received primary radiotherapy (median total dose, 46.8 Gy). Six patients (mean age, 73.5 years; 6 D) underwent primary radiosurgery (median centre dose 24, Gy) and 6 patients (6 D) admitted from other departments with recurrent tumours adjuvant radiosurgery (median centre dose, 25.5 Gy).  Findings: In 20 of the surgical cases (62.5%) complete tumour resection was achieved and the patients required no further treatment over a mean follow-up period of 9.1 years. Of the 12 patients with incomplete tumour resection, 9 (5 C, 4 D) received postoperative adjuvant radiotherapy and three patients (3 D) adjuvant radiosurgery.  In 15 (83.4%) of the 18 patients who underwent radiotherapy the tumours showed no signs of progression and the patients remained clinically unchanged over a mean period of 9.4 years. Three patients (16,6%) experienced progression of their tumour within an average period of 2.8 years.  In the 15 patients who underwent primary radiosurgery, an objective 100% tumour control rate with no evidence of progression of disease was observed.  Interpretation: The results indicate that the most effective current treatment option for patients with paragangliomas of the temporal bone is a single-stage radical tumour resection, performed in advanced tumours as an interdisciplinary neuro-otosurgical procedure. For subtotally resected or non-resectable tumours, gamma knife radiosurgery has proved to be a safe and effective treatment modality. Published online December 5, 2002  Correspondence: Dr. Walter Saringer, Neurochirurgische Universit?tsklinik, Universit?t Wien, W?hringer Gürtel 18-20, A-1090 Wien, Austria.     

Intraoperative radiotherapy for resectable and unresectable pancreatic carcinoma

Eighty patients with pancreatic carcinoma were treated by intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of 111 patients treated by surgery alone. For resectable patients, the radiation dose was 30 Gy and the average field sizes were 8 or 10 cm; for unresectable patients, these values were 20–30 Gy and 6 or 8 cm, respectively. No side effects of IORT were observed. In 49 resectable stage III patients, the IORT group (n=16) had a higher survival rate than the non-IORT group (n=33); i.e., 1-year survival rates of 44.6% vs 23% and 2-year survival rates of 37.2% vs 7.7% after surgery (P<0.05). However, there was no significant difference in survival rate between the IORT group (n=28) and the non-IORT group (n=29) in 57 resectable patients in stage IV. In unresectable patients, the IORT group (n=31) (P<0.05) had a higher survival rate than the non-IORT group (n=38) (P<0.05). The palliative effect of IORT on abdominal or back pain was evaluated in 15 patients who had such symptoms and did not undergo tumor resection. Overall, pain decreased or disappeared in 13 of these patients (87%). Offprint requests to: A. Nakao     

Long-Term Rates of Undetectable PSA with Initial Observation and Delayed Salvage Radiotherapy after Radical Prostatectomy

Background

Randomized trials have shown an improvement in progression-free survival rates with adjuvant radiation therapy (ART) after radical prostatectomy for patients with a high risk of cancer recurrence. Less is known about the relative advantages and disadvantages of initial observation with delayed salvage radiation therapy (SRT).

Objective

To examine the results of SRT in a large single-surgeon radical prostatectomy series.

Design, Setting, and Participants

From a radical prostatectomy database, we identified 859 men with positive surgical margins (SM+), extracapsular tumor extension (ECE), or seminal vesicle invasion (SVI) who chose to defer ART. Following a period of initial observation, 192 ultimately received SRT for prostate-specific antigen (PSA) progression.

Measurements

Survival analysis was performed to examine the outcomes of initial observation followed by SRT.

Results and Limitations

In patients with SM+/ECE and SVI, the 7-yr PSA progression-free survival rates with observation were 62% and 32%, respectively. Among those who had PSA progression, 56% and 26%, respectively, maintained an undetectable PSA for 5 yr after SRT. The long-term rates of undetectable PSA associated with an SRT strategy were 83% and 50% for men with SM+/ECE and SVI, respectively. In the subset of 716 men who did not receive any hormonal therapy, the corresponding long-term rates of undetectable PSA were 91% and 75%, respectively.

Conclusions

Following radical prostatectomy, initial observation followed by delayed SRT at the time of PSA recurrence is an effective strategy for selected patients with SM+/ECE. Some patients with SVI may also benefit from this strategy. However, additional prospective studies are necessary to further examine the survival outcomes following SRT.     

Radiotherapy for local progression in patients with hormone-refractory prostate cancer

PURPOSE: The aim of the present study was to investigate the effect of radiotherapy on the local progression of hormone-refractory prostate cancer. METHODS: From 1986 to 1995, 38 patients were diagnosed with local progression without distant progression after hormonal therapy at Chiba University Hospital. Eleven cases were treated with irradiation for local progression. External beam irradiation was delivered to the prostate at a dose of 50-66.6 Gy. RESULTS: In patients treated with radiotherapy, the duration from initial treatment to local recurrence was 6-80 months (mean +/- SD: 33.9 +/- 22.9 months). The follow-up period after irradiation was 7-64 months (mean +/- SD; 25.4 +/- 18.8 months). Three and 5 year cause-specific survival rates from radiotherapy were 46.2 and 23.1%, respectively. Radiotherapy had a marked effect on symptoms associated with local progression and no patients suffered from the symptoms after the radiotherapy. Complications of radiotherapy were limited. CONCLUSIONS: In patients with hormone refractory local progression without distant progression, low morbidity, low mortality radiotherapy offers a variable therapy to other palliative treatments because radiotherapy is able to control local symptoms for a long period of time.     

Recurrent Malignant Gliomas Treated with Radiosurgery

The inability to control malignant glioma results in a high incidence of local failure and poor survival. Focal therapy such as radiosurgery permits delivery of a high dose of radiation with moderate toxicity. This report summarizes the outcome of patients with recurrent malignant glioma treated with radiosurgery at University of Wisconsin Hospital, between January 1989 and December 1997, when 30 patients were treated radiosurgically. All patients had undergone and failed external beam radiotherapy (median dose of 59.4 Gy) prior to radiosurgery. All recurrences were detected by clinical deterioration and confirmed by radiographic progression. No patient was treated for radiographic progression only in the context of a screening protocol. Eight out of 30 patients underwent subtotal resection prior to radiosurgery and 3 received chemotherapy along with radiosurgery. Radiosurgery was delivered in a single fraction using a modified linear accelerator. The median tumor volume was 7.2 cm³ (range 0.42–35.1 cm³) and the median minimal tumor dose was 12 Gy at the 50–80% isodose line. Median follow-up is 70 months. The median overall survival is 8 months; the 1- and 2-year survival rates are 20% and 9%, respectively. For patients with an initial diagnosis of non-glioblastoma, the median survival is 11 months and for those with glioblastoma the median survival is 7 months. The median progression-free survival is 4 months for the entire cohort, 5 months for nonglioblastoma, and 3 months for glioblastoma. The 1-year actuarial reoperation rate after radio-surgery is 7.6%. Radiosurgery for recurrent malignant glioma may improve short-term survival for selected patients with a lower reoperation rate than brachytherapy.     

The Impact of Intermediate Time between Chemotherapy and Hypofractionated Radiotherapy to the Radiation Induced Skin Toxicity for Breast Adjuvant Treatment

To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty‐four patients with stage I–II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose‐EQD2‐ 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow‐up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late‐toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy.     

Impact of adjuvant chemoradiation for adenocarcinoma of stomach after curative gastrectomy in Chinese: A 7-year audit

Background and Aim: Adjuvant chemoradiation (CRT) after curative gastrectomy was introduced to our hospital in 1998. The present study aims to examine the impact of CRT on survival among Chinese. Methods: From our gastric cancer registry, patients who received R0 gastrectomy, with UICC stage II or above, M0 disease and ASA grades I and II were analyzed. Adjuvant CRT was offered and given if patients agreed. The regimen consisted of five cycles of 5-fluoruracil (5FU)/leucovorin chemotherapy and 45 Gy/25 fractions concurrent with cycles 2 and 3. Results: From January 1998 to December 2004, 134 patients fulfilled the criteria. Sixty had surgery alone and 74 patients received CRT after gastrectomy. One hundred and two (76%) patients received radical gastrectomy with D2 lymphadenectomy. Toxicity ≥ grade 3 was seen in 65% of patients without mortality. The overall and relapse-free 5-year survival rates were 45.8% and 42.0%, respectively. On univariate analysis, early disease stage and adjuvant CRT were associated with better prognosis. Cox regression analysis showed that adjuvant CRT (P = 0.01, HR 2.31, 95% CI: 1.4–3.9) predict better survival after adjustment with the other factors. Conclusion: In the present study, postoperative adjuvant chemoradiation is associated with better overall survival in patients with adenocarcinoma of the stomach after curative gastrectomy.     

Long-term rates of undetectable PSA with initial observation and delayed salvage radiotherapy after radical prostatectomy

BACKGROUND: Randomized trials have shown an improvement in progression-free survival rates with adjuvant radiation therapy (ART) after radical prostatectomy for patients with a high risk of cancer recurrence. Less is known about the relative advantages and disadvantages of initial observation with delayed salvage radiation therapy (SRT). OBJECTIVE: To examine the results of SRT in a large single-surgeon radical prostatectomy series. DESIGN, SETTING, AND PARTICIPANTS: From a radical prostatectomy database, we identified 859 men with positive surgical margins (SM+), extracapsular tumor extension (ECE), or seminal vesicle invasion (SVI) who chose to defer ART. Following a period of initial observation, 192 ultimately received SRT for prostate-specific antigen (PSA) progression. MEASUREMENTS: Survival analysis was performed to examine the outcomes of initial observation followed by SRT. RESULTS AND LIMITATIONS: In patients with SM+/ECE and SVI, the 7-yr PSA progression-free survival rates with observation were 62% and 32%, respectively. Among those who had PSA progression, 56% and 26%, respectively, maintained an undetectable PSA for 5 yr after SRT. The long-term rates of undetectable PSA associated with an SRT strategy were 83% and 50% for men with SM+/ECE and SVI, respectively. In the subset of 716 men who did not receive any hormonal therapy, the corresponding long-term rates of undetectable PSA were 91% and 75%, respectively. CONCLUSIONS: Following radical prostatectomy, initial observation followed by delayed SRT at the time of PSA recurrence is an effective strategy for selected patients with SM+/ECE. Some patients with SVI may also benefit from this strategy. However, additional prospective studies are necessary to further examine the survival outcomes following SRT.     

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer

PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.     

Management of vestibular schwannoma by fractionated stereotactic radiotherapy and associated cerebrospinal fluid malabsorption

OBJECT: The goal of this study was to investigate outcomes in patients with vestibular schwannoma (VS) who were treated with fractionated stereotactic radiotherapy (SRT). METHODS: One hundred one patients with VS were treated with fractionated SRT at a radiation level of 40 to 50 Gy administered in 20 to 25 fractions over a 5- to 6-week period. The median tumor size in these patients was 19 mm (range 3-40 mm), and 27 tumors were larger than 25 mm. Patients were consistently followed up using magnetic resonance imaging every 6 months for 5 years in principle. The median follow-up period was 45 months. The actuarial 5-year rate of tumor control (no growth > 2 mm and no requirement for salvage surgery) was 91.4% (95% confidence interval 85.2-97.6%). Three patients with progressive tumors underwent salvage tumor resection. The actuarial 5-year rate of useful hearing preservation (Gardner-Robertson Class I or II) was 71%. The observed complications of fractionated SRT included transient facial nerve palsy (4% of patients), trigeminal neuropathy (14% of patients), and balance disturbance (17% of patients). No new permanent facial weakness occurred after fractionated SRT. Eleven patients (11%) who had progressive communicating hydrocephalus (cerebrospinal fluid malabsorption) and no evidence of tumor growth after fractionated SRT required a shunt. The symptoms of this type of hydrocephalus were similar to those of normal-pressure hydrocephalus and occurred 4 to 20 months (median 12 months) after fractionated SRT. The mean size (+/- standard deviation) of tumors causing symptomatic hydrocephalus (25.5 +/- 7.8 mm) was significantly larger than that of other tumors (18.2 +/- 8.7 mm) (p = 0.011). Only four of the 72 patients with tumors smaller than 25 mm in maximum diameter received a shunt. CONCLUSIONS: Fractionated SRT resulted in an excellent tumor control rate, even for relatively large tumors, and produced a high rate of hearing preservation that was comparable to the best results of single-fraction radiosurgery. The progression of communicating hydrocephalus should be monitored closely, particularly in patients harboring a large VS.     

PRE-OPERATIVE CHEMORADIOTHERAPY IN LOCALLY ADVANCED RECTAL CANCER

Background : The aim of the present study was to investigate the effectiveness and toxicity of pre-operative chemoradiation in locally advanced rectal cancer (T₃–T₄). Methods : Forty-seven patients were assessed (38 T₃ and nine T₄ tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy in 25 fractions over 5 weeks. Bolus 5-fluorouracil (5-FU) was delivered 500 mg/m ² on days 1, 2, 3 and days 22, 23, 24. Total mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4–6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. Results : All patients undergoing chemoradiation completed therapy as planned, with no treatment-related interruptions. The regimen had a low acute toxicity profile with an estimated 50% or greater response in 38 out of 47 patients (four patients had complete responses). Forty-three (97%) of 44 patients who underwent surgery were operable. Patients who were operated on between 4 and 7 weeks had a statistically better response then those who were operated on after 7 weeks (P = 0.013; Fisher’s exact test). Eight of 10 patients who were considered to be inoperable prior to the treatment underwent total mesorectal excision with negative radial margins. Anastomotic leakage occurred in four patients (9%); one required surgical intervention. Wound infection occurred in three patients (6%); one patient required re-exploration for haemorrhage. Delayed complications occurred in three patients (6%); one requiring surgery for a stomal stricture. After a median follow-up of 20 months, two patients (4%) had developed local recurrence. Conclusion : The pre-operative chemoradiation regimen employed had a low acute toxicity profile and all patients completed therapy. The majority of patients considered inoperable prior to receiving this treatment underwent successful excision. Appropriately fractionated pre-operative chemoradiotherapy is a reasonable option in this disease and deserves further evaluation.     

Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica

ObjectiveSurvival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP).Materials and methodsRetrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥ 8, pathologic stage ≥ pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4 ng/ml.A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression.ResultsMean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients.Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10 years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15 years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15 years were 99.1%, 98.1% and 96.6%.Only time to BR < 24 months (HR = 2.55, P = .01) was identified as an independent risk factor for RFS after SRT.ConclusionsIn these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP + SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence > 24 months responded better to rescue treatment.     

Enlargement of a vestibular schwannoma after stereotactic radiotherapy

Summary.  Background: Radiosurgery has been increasingly advocated as a primary treatment for vestibular schwannoma (VS), and recently fractionation of the dose has been proposed as a method to decrease the risk of radiation injury when treating larger tumors.  Method: The authors describe a 48-year-old woman who presented with right-sided hearing loss and new-onset tinnitus, with a progressive decrease in facial sensation. The diagnosis of a large right cerebellopontine angle VS was made on magnetic resonance imaging (MRI). The patient was treated with a course of fractionated stereotactic radiotherapy (SRT) (5 treatments of 4 Gy to the 90% isodose line over a 3-week period).  Findings: Six months after the initiation of therapy, her symptoms increased, and a repeat MRI scan demonstrated that her tumor had increased in size, producing significant brainstem compression. She then underwent complete surgical resection of the tumor, with resolution of her symptoms.  Interpretation: Stereotactic radiosurgery has been effective in controlling small VSs with low complication rates. Larger tumors pose a risk for increasing in size and producing symptoms from mass effect with SRT. There are at present limited data demonstrating safety and efficacy of fractionated SRT for the treatment of larger tumors. Published online December 5, 2002  Correspondence: William T. Couldwell, M.D., Ph.D., Department of Neurosurgery, The University of Utah, Suite 3B409, 30 North 1900 East, Salt Lake City, UT 84132-2303.     

Improved toxicity profile following high-dose postprostatectomy salvage radiation therapy with intensity-modulated radiation therapy

Background

With salvage radiation therapy (SRT) in the postprostatectomy setting, the need to deliver sufficient radiation doses to achieve a high probability of tumor control is balanced with the risk of increased toxicity. Intensity-modulated radiation therapy (IMRT) in the postprostatectomy salvage setting is gaining interest as a treatment strategy.

Objective

Compare acute and late toxicities in patients treated with IMRT and three-dimensional conformal radiation therapy (3D-CRT) in the postprostatectomy salvage setting.

Design, setting, and participants

A total of 285 patients who were treated at our institution between 1988 and 2007 with SRT after radical prostatectomy for biochemical recurrence were identified. All medical records were reviewed and toxicity recorded. Median follow-up was 60 mo.

Intervention

All patients were treated with SRT with either 3D-CRT (n = 109) or IMRT (n = 176). A total of 205 patients (72%) were treated with doses ≥70 Gy.

Measurements

Late gastrointestinal (GI) and genitourinary (GU) toxicities were recorded using the Common Terminology Criteria for Adverse Events v. 3.0 definition.

Results and limitations

The 5-yr actuarial rates of late grade ≥2 GI and GU toxicity were 5.2% and 17.0%, respectively. IMRT was independently associated with a reduction in grade ≥2 GI toxicity compared with 3D-CRT (5-yr IMRT, 1.9%; 5-yr 3D-CRT, 10.2%; p = 0.02). IMRT was not associated with a reduction in risk of grade ≥2 GU toxicity (5-yr IMRT, 16.8%; 5-yr 3D-CRT, 15.8%; p = 0.86), urinary incontinence (5-yr IMRT, 13.6%; 5-yr 3D-CRT, 7.9%; p = 0.25), or grade 3 erectile dysfunction (5-yr IMRT, 26%; 5-yr 3D-CRT, 30%; p = 0.82). Of patients who developed late grade ≥2 GI or GU toxicity, 38% and 44%, respectively, experienced resolution of their symptoms prior to the last follow-up.

Conclusions

Our experience with high-dose IMRT in the postprostatectomy salvage setting demonstrates that the treatment can be delivered safely with an associated reduction in late GI toxicity.