Long-term outcomes of intraluminal brachytherapy in combination with external beam radiotherapy for superficial esophageal cancer

Background

The aim of this study was to assess the long-term outcomes of combining high-dose-rate intraluminal brachytherapy (IBT) with external beam radiotherapy (EBRT) for superficial esophageal cancer (SEC).

Methods

From 1992 to 2002, 87 patients with T1N0M0 thoracic esophageal cancer received IBT in combination with EBRT. Of these, 44 had mucosal cancer and 43 had submucosal cancer. For patients with tumor invasion within the lamina propria mucosa, IBT alone was performed (n?=?27). IBT boost following EBRT was performed for patients with tumor invasion in the muscularis mucosa or deeper (n?=?60). No patient received chemotherapy.

Results

The median follow-up time was 94?months. For mucosal cancer, the 5-year locoregional control (LRC), cause-specific survival (CSS) and overall survival (OS) rates were 75, 97 and 84%, respectively, and 49, 55 and 31%, respectively, for submucosal cancer. Tumor depth was a significant factor associated with LRC (p?=?0.02), CSS (p?<?0.001) and OS (p?<?0.001) by univariate analysis. Multivariate analysis revealed that tumor depth was the only significant predictor for OS (p?=?0.003). Late toxicities of grade 3 or higher in esophagus, pneumonitis, pleural effusion and pericardial effusion were observed in 5, 0, 0 and 1 patients, respectively. Grade ??3 events of cardiac ischemia and heart failure after radiotherapy were observed in 9 patients, and history of heart disease before radiotherapy was the only significant factor (p?=?0.002).

Conclusion

There was a clear difference in outcomes of IBT combined with EBRT between mucosal and submucosal esophageal cancers. More intensive treatment should be considered for submucosal cancer.     

Results of high dose-rate brachytherapy boost before 2D or 3D external beam irradiation for prostate cancer

Background and purpose

To evaluate biochemical control and treatment related toxicity of patients with localized adenocarcinoma of the prostate treated with high dose-rate brachytherapy (HDRB) combined with conventional 2D or 3D-conformal external beam irradiation (EBI).

Material and methods

Four-hundred and three patients treated between December 2000 and March 2004. HDRB was delivered with three fractions of 5.5-7 Gy with a single implant, followed by 45 Gy delivered with 2D or 3D conformal EBI.

Results

The median follow-up was 48.4 months. Biochemical failure (BF) occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. Mean time to relapse was 13 and 26 months, respectively. The 5-year BF free survival using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively; using Phoenix criteria, 92.4%, 88.0% and 85.3%, respectively. The only predictive factor of BF in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules detected by digital palpation, and patients younger than 60 years presented a higher chance of failure using Phoenix criteria only.

Conclusions

Treatment scheme is feasible and safe with good efficacy.     

Derivation of isoeffect dose rate for low-dose-rate brachytherapy and external beam irradiation

Purpose: The combination of external beam irradiation and brachytherapy has been used effectively in the management of many malignancies. Brachytherapy dose is typically prescribed to an isodose rate line, from which the implant duration is derived. In this study, the linear-quadratic model is used to derive the brachytherapy dose rate at which biological effectiveness is equivalent to that of external beam irradiation.

Methods and Materials: Relative effectiveness per unit dose (RE) for brachytherapy was based on Dale’s formalism. Isoeffect dose rate, defined as the brachytherapy dose rate at which the biological effectiveness is equivalent to that of external beam irradiation, was derived.

Results: The functional dependencies of brachytherapy RE on dose rate, /β ratio, and implant duration were investigated. The isoeffect dose rate depends only on the dose per fraction, sublethal damage repair (SLDR) constant, and the implant duration. The isoeffect dose rate does not depend on /β ratio. For sufficiently long implant duration > 10–15 hours, the value for isoeffect dose rate approaches a constant value around 40 to 50 cGy/hr.

Conclusion: The isoeffect dose rate may be useful in treatment planning and optimization for low-dose-rate (LDR) brachytherapy, especially when brachytherapy is used in combination with external beam irradiation.     

Quality of life after surgery, external beam irradiation, or brachytherapy for early-stage prostate cancer

BACKGROUND: The primary treatments for clinically localized prostate cancer confer equivalent cancer control for most patients but disparate side effects. In the current study, the authors sought to compare health-related quality of life (HRQOL) outcomes after the most commonly used treatments. METHODS: A total of 580 men completed the Medical Outcomes Study Short Form-36, the University of California-Los Angeles (UCLA) Prostate Cancer Index, and the American Urological Association Symptom Index before and through 24 months after treatment with radical prostatectomy (RP), external beam radiation therapy (EBRT), or brachytherapy (BT). RESULTS: General HRQOL did not appear to be affected by treatment. Obstructive and irritative urinary symptoms were more common after BT (P<.001). Urinary control and sexual function were better after EBRT than BT (P<.001 and P=.02, respectively) and better after BT than RP (P<.001 and P=.01, respectively). Among potent men, recovery of sexual function was best after EBRT and was equivalent after bilateral nerve-sparing surgery or BT. Sexual bother was more common than urinary or bowel bother after all 3 treatments. Bowel dysfunction was more common after EBRT or BT than RP (P<.001). CONCLUSIONS: In the current study, treatment for localized prostate cancer was found to differentially affect HRQOL outcomes. Urinary control and sexual function were better after EBRT, although bilateral nerve-sparing surgery diminished these differences among potent men undergoing RP. BT caused more obstructive and irritative symptoms, while both forms of radiation caused more bowel dysfunction. These results may inform medical decision-making in men with localized prostate cancer.     

High-dose-rate brachytherapy without external beam irradiation for locally advanced prostate cancer.

BACKGROUND AND PURPOSE: High-dose-rate brachytherapy (HDR-BT) had been used only in combination with external beam irradiation (EBI) until our previously reported first trial of HDR-BT alone without EBI. The purpose of the current report is to evaluate the feasibility, toxicity and efficacy of this regimen, with more patient accrual and longer follow-up. MATERIAL AND METHODS: From 1995 through 2004, 111 patients with localized prostate cancer were treated with HDR-BT without EBI. Fifteen patients were considered as low-risk, 28 as intermediate-risk, and 68 as high-risk. The prescribed dose was 48 Gy/8 fractions/5 days or 54 Gy/9 fractions/5 days. Median follow-up time was 27 months (range 5-119). RESULTS: All the patients completed the treatment regimen. The 3- and 5-year PSA failure-free rates were 83% and 70%, and the local control rates 100% and 97%. The maximum toxicities observed were Grade 3 by CTCAE v3.0 (6 acute, 1 chronic). CONCLUSIONS: HDR-BT without EBI was feasible and its toxicity acceptable. Short-term tumor control was promising, even for locally advanced cases. More patient accrual and longer follow-up are needed to confirm the efficacy of this novel approach.     

Contemporary external beam radiotherapy boost or high dose-rate brachytherapy boost for cervical cancer: a propensity-score-matched,nationwide, population-based cohort study

To estimate the survival effects of contemporary external beam radiotherapy (EBRT) boost modalities (intensity-modulated radiation therapy or volumetric modulated arc therapy) and high dose-rate brachytherapy (HDR-BT) boost in patients with cervical cancer (CC). Patients who had been diagnosed as having CC were recruited from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze the all-cause mortality of patients who received standard whole-pelvis irradiation with different boost modalities. The matching process yielded a final cohort of 1,630 patients (815 in the EBRT boost and HDR-BT boost groups, respectively) eligible for further analysis. The multivariate Cox regression analyses indicated that the adjusted hazard ratio (95% confidence intervals) for EBRT boost compared with HDR-BT boost was 1.62 (1.43-1.84). Multivariable analysis revealed that the independent poor prognostic factors of all-cause mortality among patients with CC were adenocarcinoma, no chemotherapy, Charlson comorbidity index score ≥ 1, age ≥ 60 years, and advanced International Federation of Gynecology and Obstetrics stage. HDR-BT boost may be more beneficial than contemporary EBRT boost in selected patients with CC.     

Endobronchial brachytherapy in combination with external beam irradiation in obstructing malignant bronchial tumors

Endobronchial brachytherapy is commonly used in the palliative management of malignant airway obstructions. In the present study, we describe the results of brachytherapy (mean dose of 18 Gy), used in combination with external beam irradiation (mean dose of 50 Gy) in 30 patients who had primary bronchogenic carcinoma of the lung. The extent of airway obstruction was determined according to symptoms and by bronchoscopy. We found symptoms improved in nearly 37% of patients and 21 of 30 patients (70%), evaluated with bronchoscopy, showed a response when evaluated 3 to 6 months after brachytherapy. This endobronchial technique appeared to be a well-tolerated procedure with a low rate of acute toxicity. The immediate complication rate was 13%, during the follow-up 3 deaths were related to treatment, of which 2 were fatal haemoptysis (12 and 18 months after irradiation). We conclude that the combination of endobronchial brachytherapy with external beam irradiation may be useful and needs further comparisons with other irradiation procedures.     

High dose rate brachytherapy before external beam irradiation in inoperable oesophageal cancer.

To induce fast relief of dysphagia in patients with oesophageal cancer high dose rate (HDR) brachytherapy was applied before external radiotherapy in a prospective study. Seventy-four patients with inoperable oesophageal cancer (36 squamous cell, 38 adenocarcinoma) were treated with a combination of 10 Gy HDR brachytherapy, followed by 40 Gy in 4 weeks external beam radiotherapy (EBRT), starting 2 weeks later. Tumour response, as measured by endoscopy and/or barium swallow, revealed complete remission in 21 and partial response in 38 patients (overall response rate 80%). Improvement of dysphagia was induced by brachytherapy within a few days in 39%, and achieved at the end of treatment in 70% of patients. Further weight loss was prevented in 39 of the 59 patients who presented with weight loss. Pain at presentation improved in 12 out of 25 patients. Median survival was 9 months. No differences in either response rate or survival were found in squamous cell or adenocarcinoma. Side-effects were either acute with minimal discomfort in 32 (42%) or late with painful ulceration in five patients (7%), occurring after a median of 4 months. A fistula developed in six patients, all with concurrent tumour. In conclusion, brachytherapy before EBRT was a safe and effective procedure to induce rapid relief of dysphagia, especially when combined with EBRT.     

The preservation of potency after external beam irradiation for prostate cancer

A prospective study was undertaken to assess the relationship of potency before irradiation to the chance of maintaining potency after irradiation. For men who were truly sexually active prior to radiation (defined as having intercourse three or more times per month and having full erections) the chance of maintaining potency was 73%. For men who were borderline sexually active, the chance of maintaining potency was markedly decreased to 40-46%. Thus, the truly potent patient has a greater chance of maintaining potency than the borderline potent patient. This information can be helpful to oncologists as they counsel recently diagnosed prostate cancer regarding the optimal method of cancer management.     

Combination of external beam irradiation and high-dose-rate intraluminal brachytherapy for inoperable carcinoma of the extrahepatic bile ducts

PURPOSE: To assess the feasibility and therapeutic benefits of a combination of external beam radiotherapy (EBRT) and high-dose-rate intraluminal brachytherapy (ILBT) for treating patients with inoperable carcinoma of the extrahepatic bile ducts. METHODS AND MATERIALS: Of 31 patients who received RT at the Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Korea between 1986 and 1995, 17 patients underwent EBRT alone (Group 1) and 14 patients were treated with EBRT in combination with high-dose-rate ILBT (Group 2). After external drainage, EBRT was delivered with a total dose ranging from 36 to 55 Gy (median 50.4) in both groups. High-dose-rate ILBT for the patients in Group 2 was performed using a high-intensity (192)Ir source (Gamma-med remote afterloading system) within the expandable intrabiliary prosthesis (Gianturco stent), inserted transhepatically at the site of the obstruction. The radiation dose of the high-dose-rate ILBT was prescribed at 1.5 cm from the center of the source with a single daily dose of 5 Gy to a total of 15 Gy given in three fractions. The response rate, patterns of treatment failure, treatment morbidity, and survival data in the two groups were compared. RESULTS: Although locoregional recurrence was the most common pattern of failure in both groups, no statistically significant difference was found in the recurrence rates between those who did and did not receive ILBT (53% for Group 1 vs. 36% for Group 2; p > 0.05). However, a prolongation of the median time to tumor recurrence was observed in the Group 2 patients (5 months for Group 1 vs. 9 months for Group 2; p = 0.06). When the EBRT dose delivered was >50 Gy, most patients experienced various degrees of GI symptoms, but the frequency of radiation-induced complications in the two groups was similar. No enhancement in treatment morbidity was attributed to the addition of high-dose-rate ILBT to EBRT. With a median follow-up of 12 months, the overall actuarial 2-year survival rate for Group 2 patients was significantly better than that for Group 1 patients (0% for Group 1 vs. 21% for Group 2; p = 0.015). CONCLUSION: Given these observations, we believe that the combined use of EBRT and high-dose-rate ILBT is a beneficial, relatively safe, and effective method of improving the treatment outcome in selected patients with inoperable carcinoma of the extrahepatic bile ducts.     

Adjuvant high-dose-rate brachytherapy after external beam radiotherapy in nasopharyngeal carcinoma.

PURPOSE: To compare the local control and survival rates obtained with either external beam radiation therapy (ERT) and adjuvant high-dose-rate (HDR) brachytherapy (BRT) or ERT alone in patients with nasopharyngeal cancer. METHODS AND MATERIALS: Between December 1993 and December 1999, 144 patients (106 male, 38 female) with the diagnosis of nasopharyngeal cancer were treated with either ERT and adjuvant HDR BRT (Group A) or ERT alone (Group B) at our department. BRT was not applied in 38 patients for the following reasons: (1) Unit was unavailable (n = 13), (2) Patient was younger than 18 years (n = 17), (3) Patient received accelerated hyperfractionated ERT (n = 6), and (4) Patient refused BRT (n = 2). The median age for whole group was 43 (range: 9-82 years). According to the AJCC-1997 staging system, there were 11 (7.6%), 35 (24.3%), 38 (26.4%), and 60 (41.7%) patients in Stage I, II, III, and IV, respectively. There were 57 (39.6%) patients with T1, 41 (28.5%) with T2, 20 (13.9%) with T3, and 26 (18.1%) with T4 tumors. Histopathologic diagnosis was WHO 2-3 in 137 (95.2%) patients. ERT doses ranged between 58.8 and 74 Gy (median: 66 Gy). There were significantly more patients with young age, N2 status, and Stage III disease in Group B and with Stage II disease in Group A. Significantly more patients received chemotherapy in Group B. BRT with an HDR 192Ir microSelectron afterloading unit was delivered in 106 patients at the conclusion of ERT using a single-channel nasal applicator. Dose was prescribed at 1 cm from the source, and total dose of 12 Gy in 3 fractions on 3 consecutive days was given immediately after ERT. Besides radiotherapy, 82 (56.9%) patients received cisplatin-based chemotherapy, as well. Follow-up time ranged between 12 and 80 months (median: 32 months). RESULTS: The two groups were comparable in terms of local recurrence, locoregional failure, regional failure, and rate of distant metastasis. Local failure was observed in 11 (10.3%) out of 106 patients in Group A and in 2 (5.2%) out of 38 patients in Group B (p > 0.05). Three-year disease-free survival rate was 67% and 80% (p = 0.07), respectively, and 3-year local recurrence-free survival rate was 86% and 94% (p = 0.23) for Group A and B, respectively. Multivariate analysis showed that advanced nodal status and male gender were significantly unfavorable factors for disease-free survival, and Stage II disease was unfavorable for local recurrence-free survival. The administration of adjuvant HDR BRT was not an independent prognostic factor in multivariate analysis. Out of 106 patients, 42 (39.7%) experienced nasal congestion, transient nasal obstruction, and/or fibrinous exudate in response to antihistaminic treatment. Only three (2.8%) patients experienced nasal synechy related, most probably, to the BRT. Five patients developed severe neural complications; only one out of five was observed in Group A. No severe complication attributed directly to BRT was detected. CONCLUSION: The acute and late morbidity of adjuvant HDR BRT is acceptable with our treatment scheme, but we did not find any local control difference between our patients treated with adjuvant BRT after ERT and ERT alone. We believe that the exact role of adjuvant HDR BRT can be elucidated only by prospective randomized studies.     

192Ir low dose rate brachytherapy for boosting locally advanced prostate cancers after external beam radiotherapy: a phase II trial.

BACKGROUND AND PURPOSE: To evaluate on 201 locally advanced prostatic cancers prospectively treated in a phase II trial, the efficacy of a combination of external beam radiotherapy (39.6 Gy) and (192)Ir low dose rate brachytherapy (Bt) (40-45 Gy). PATIENTS AND METHODS: Sixty-four patients were included in the intermediate prognosis group with only one of the following adverse factors (PSA > 10 ng/ml, Gleason score > or = 7 or clinical stage > or =T2b) and 137 in the unfavourable group when at least two of these factors were present. RESULTS: The actuarial 4 years biochemical no evidence of disease is 82.8% for the entire population. It is, respectively, 97 and 76% in the intermediate and unfavourable prognosis groups (P < 0.0001). Grade > or =3 late urinary complications occurred in 13 patients (6.5%). Eight patients (4%) presented late grade 2 rectal complications but no grades 3-5 was observed. CONCLUSIONS: Even if an alpha/beta of 1.5-3 Gy theoretically favours the use of a high dose rate mode of irradiation, the early results presented here are as good as those reported for similar groups of patients with high dose rate treatments. Late toxicity is identical but our urinary toxicity is within the less favourable and rectal toxicity within the most favourable results. We can postulate that while inducing very high hyperdosage regions (V150) mainly focused on the peripheral zone, most of the Bt techniques consist of a more ablative treatment. Many of the radiobiological studies on Bt did not in fact take into account the heterogeneity of irradiation inside the CTV. This study highlights the need to explore pulsed dose rate therapies, permanent implant and new available radioisotopes such as (169)Ytterbium that will offer the safety of low and lower dose rates. The actual late toxicity of the different Bt techniques is not yet inexistent indeed.     

Repeat high-dose external beam irradiation for in-breast tumor recurrence after previous lumpectomy and whole breast irradiation

PURPOSE: To determine whether excision of an in-breast tumor recurrence (IBTR) plus 5000 cGy in 25 fractions to the new operative area is both tolerated and effective as treatment for an IBTR after previous lumpectomy and whole breast irradiation.METHODS AND MATERIALS: Thirty-nine women with an IBTR after lumpectomy and breast irradiation for invasive carcinoma (n = 31) or ductal carcinoma in situ (n = 8) were treated with excision of the IBTR and radiotherapy (RT), 5000 cGy in 25 fractions, to the operative area using electrons of appropriate energy. The interval from completion of the first course of RT to diagnosis of the IBTR ranged from 16 to 291 months (median 63).RESULTS: The repeat course of RT to the new operative area was well tolerated in all patients, and no late sequelae occurred other than skin pigmentation changes. Eight patients, including 2 with suspicious bone scans at the time of IBTR, developed distant metastases, and 7 died 21-71 months (median 48) after retreatment. One patient was alive with distant metastases at 27 months after retreatment. Four of the 8 patients who developed distant metastases also had a second IBTR, and 3 died with persistent disease in the breast. An additional 4 patients, for a total of 8, had a second IBTR. Three were alive and free of disease after mastectomy, and 1 was alive and free of disease after mastectomy and additional RT for chest wall recurrence. An additional patient developed recurrence in the axilla 9 months after reirradiation and was treated with surgery; she died free of disease at 63 months. One patient underwent mastectomy for suspected persistent disease 2 months after completion of repeat RT; no evidence of recurrent tumor was found in the removed breast. Thus, 30 women (76.9%) had an intact breast free of tumor at death or at last follow-up 1-180 months (median 51.5) after reirradiation. Using the Kaplan-Meier life table analysis, the estimated overall and disease-free 5-year survival rate for the 39 patients was 77.9% and 68.5%, respectively.CONCLUSION: For select patients with an IBTR after lumpectomy and breast irradiation, excision of the IBTR followed by repeat external beam RT to the operative area may be an acceptable alternative to mastectomy.     

The role of external beam in brachytherapy

In this paper we put forward the claim that the combination of low dose-rate brachytherapy (BRT) and fractionated external-beam radiotherapy (EBRT) may, when planned to take advantage of the relative advantages of each of these two modalities, result in enhanced tumor dose with no penalties to organs at risk. The concept of iso-effective dose (IED) serves the role of common currency for fusing BRT and EBRT and, for evaluation purposes, converting back the resulting IED distribution into a biologically equivalent plan delivered by any single modality. If we accept this view, there are further questions that must be answered regarding practical matters. We show how to deal with these questions by describing an actual patient plan.     

Residual, unresectable, or recurrent colorectal cancer: external beam irradiation and intraoperative electron beam boost +/- resection

While combinations of external beam radiation (XRT) and surgery decrease pelvic recurrence and improve survival in the subgroups with residual disease (postop XRT) or initially unresectable disease (preop XRT), local recurrence is still unacceptably high, and survival could be improved. In view of this, pilot studies were instituted at Massachusetts General Hospital in which 32 patients received the standard previous treatment of external beam irradiation and surgery but in addition had an intraoperative electron beam boost of 1000-1500 rad to the remaining tumor or tumor bed. For the 16 patients who presented with unresectable primary lesions, the addition of intraoperative radiotherapy has resulted in a total absence of local recurrence with a minimum 20 month follow-up, and survival rates are statistically better than for the previous group treated with only external beam irradiation and surgical resection. In the group with residual disease, again there have not been any local recurrences in the 7 patients who received all treatment modalities versus 54% and 26% for the group with gross and microscopic residual treated with only external beam techniques. The remaining 9 patients presented with recurrent unresectable lesions--3 are alive (2 NED) at greater than or equal to 3 years.     

HDR-brachytherapy boost for residual tumour after external beam radiotherapy in patients with tracheal malignancies.

Seven inoperable patients with tracheal neoplasms received a high dose rate (HDR) brachytherapy boost (median 15 Gy, single dose 3-5 Gy) for residual tumour after external beam radiotherapy (median 50 Gy, 5 x 2 Gy/week). The median actuarial survival was 34.3 months. The 1-, 2- and 3-year actuarial survival rates were 85.7%, 85.7% and 32%. Local control was obtained in 5/7 patients. Late toxicity occurred in three patients (stenosis n = 2, hemorrhage n = 1). Our data indicate, that a HDR brachytherapy boost is effective and feasible.