Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

Purpose

The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy.

Patients and methods

Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83?%). The aim of the hyperthermia treatment was to heat the prostate to 41–43?°C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir +?2 ng/ml).

Results

The median age was 71 years (range 62–83 years), the median initial PSA level was 16.3 ng/ml (range 6.37–64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044–25.346 ng/ml). The median follow-up was 13 months (range 4–48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan–Meier estimate of biochemical control after salvage treatment was 74?%. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir <?0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients.

Conclusion

IHT in combination with salvage HDR brachytherapy is a well tolerated and effective treatment.     

Präoperative Bestrahlung mit interstitiellem Radiohyperthermie-Boost bei Mammatumoren ≥3 cm

Aim

The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia.

Patients and Methods

One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy¹⁹²Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 × 2 Gy/week. Local hyperthermia with 43.5–44.5°C over 60 minutes was delivered immediately before interstitial radiotherapy.

Results

One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases.

Conclusion

In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.     

Interstitial hyperthermia of the prostate in combination with brachytherapy

Objective

A retrospective study to evaluate the feasibility and toxicity of interstitial hyperthermia (IHT) combined with high-dose-rate (HDR) brachytherapy as the initial treatment for low- and intermediate-risk prostate cancer, and as a salvage therapy in previously irradiated patients with local recurrence.

Patients and methods

Between 18 December 2008 and 5 September 2012, 73  prostate cancer patients were treated with interstitial HDR brachytherapy of the prostate combined with IHT. In 54 patients this was the initial therapy for prostate cancer, while the other 19 were treated for local recurrence after previously undergoing external beam radiotherapy (EBRT). Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 within 3 months after treatment.

Results

Median follow-up was 15 months (range 3–46). The combination of HDR brachytherapy and IHT was well tolerated. The toxicity profile was similar to that of HDR brachytherapy when not combined with hyperthermia. The most common minor complications were urinary frequency (grade 1: 37?%; grade 2: 22?%), nocturia (three times per night: 29?%; four- or more times per night: 20?%) and transient weakening of the urine stream (grade 1: 36?%; grade 2: 11?%). No early rectal complications were observed in the patient group and the severity of genitourinary toxicity was only grade 1–2.

Conclusion

Early tolerance of IHT in combination with HDR brachytherapy is good. Further prospective clinical studies should focus on the effects of combining IHT with HDR brachytherapy and the influence of this adjuvant therapy on biochemical disease-free survival, local control and overall survival.     

Phase-I/II-Studie zur lokalen Hyperthermie zervikaler N2/N3-Lymphknotenmetastasen

Background

Patients with advanced lymph node metastases from head and neck tumors at stage N2/N3 (i. e. UICC IV) present a difficult therapeutic problem. Despite combined radio-chemotherapy and hyperfractionated and/or accelerated fractionation regimens, local control of these tumors remains unsatisfactory. For this reason, the value of local radiowave/microwave hyperthermia was examined for this patient group in a phase I/II study.

Patients and Method

Fifty patients with primary advanced, recurrent or persistent N2/N3 lymph node metastases were treated with microwave hyperthermia in addition to their standard therapy (radiotherapy or radiochemotherapy). For the thermometry, closed-end catheters were implanted in the cervical lesions under CT monitoring. Temperature/time and temperature/position curves were analysed with regard to power density, effective perfusion, tissue depth index temperatures T₉₀, T₅₀, T₂₀, cum min T₉₀≥40.5°C, and equ min T₉₀ at 43°C. Radiation dose, total irradiation time and chemotherapy were also recorded as therapy parameters. Repeated CT scans for assessing response were taken for a subgroup of 32 patients following primary potentially curative radiotherapy (with and without chemotherapy) and local hyperthermia. All therapy parameters were subjected to a variance analysis with regard to response.

Results

At a tissue depth of 3 cm, relative and absolute power densities were on average of 50% less than at the surface. Therapeutic temperature increases of more than 4°C (i.e. more than 41°C) were not reached at tissue depths greater than 5 cm. The effective perfusion under local hyperthermia is significantly higher than under basal conditions. The mean T₉₀ value was 39.9°C, and the mean T₂₀ value was 42.3°C, T₉₀, cum min T₉₀≥40.5°C, equ min T₉₀ 43°C, radiation dose and total irradiation time have a significant influence on response. The tumor volume correlates negatively with response, and this results in the thermal gradients correlating negatively with response and survival. The quality of the temperature distribution, represented by the value of cum min T₉₀≥40.5°C, showed a tendency to correlate positively with the survival in the subgroup of patients who underwent primary therapy. However, the long-term prognosis after 3 years remained bad for this patient group, with a survival rate of around 20%, although local control of primary treated patients was achieved in around 65%.

Conclusions

Patients with advanced lymph node metastases that increase 4 cm in diameter have an extremely bad prognosis which has not been significantly changed by modern radio-chemotherapy. For a specific patient group with lymph nodes between 4 and 7 cm diameter, local hyperthermia can improve the results. However, the physical limitations of the method are clear and further developments are required.     

Protocol-based image-guided salvage brachytherapy

Purpose

To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects.

Patients and methods

Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005–2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V₁₀₀ >?95?%) simultaneously respecting the protocol-based dose volume constraints for the urethra (D_0.1 cc <?130?%) and the rectum (D_2 cc <?50–60?%) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities—particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival.

Results

We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1?% (2/18) and 16.7?% (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17?% (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1?%. The overall survival at 3 years was 88.9?%; 22?% (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8–77 months).

Conclusion

Salvage PDR-brachytherapy of the prostate following local failure after radiation therapy is a treatment option with a low rate of genitourinary side effects and no late gastrointestinal side effects. The treatment efficacy in the first 3 years is promising.     

Effect of concurrent chemotherapy and hyperthermia on outcome of preoperative radiotherapy of high-risk soft tissue sarcomas

Background and purpose

As treatment results for high-risk soft tissue sarcoma are still disappointing, treatment intensification is warranted. We performed a retrospective analysis of multimodal preoperative treatment to evaluate the additional effect of concurrent chemotherapy and/or locoregional hyperthermia in comparison to radiotherapy alone.

Patients and methods

Between 1999 and 2011, 28 patients were treated with neoadjuvant radiotherapy to a median 45 Gy for high-risk soft tissue sarcoma. All tumors were deep-seated and grade 2 or 3, 86% (n?=?24) larger than 5 cm. Multimodal treatment (n?=?12) consisted of ifosfamide (n?=?7), locoregional hyperthermia (n?=?3), or both modalities (n?=?2) concurrent to radiotherapy.

Results

Prognostic factors (grade, size, histology, location) were balanced in the groups with and without concurrent multimodal treatment. There was a significant improvement of disease-specific survival (100% vs. 70% at 3 years, p?=?0.03) with multimodal treatment. Distant metastases-free survival was influenced, but was not statistically significant. Local control and disease-free survival did not differ in the two groups.

Conclusion

Our data suggest that multimodal treatment with ifosfamide and/or locoregional hyperthermia in combination with neoadjuvant radiotherapy might improve outcome in high-risk soft tissue sarcomas.     

Concomitant adjuvant chemo-radiation therapy with anthracyclinebased regimens in breast cancer: a single centre experience

Purpose

This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline (AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the impact of treatment interruptions and the feasibility of this uncommon therapeutic approach.

Materials and methods

From September 2002 to December 2007, 60 patients were treated at our Centre. The mean age at presentation was 48.5 (range 38?C64) years. All patients underwent conservative surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46?C52 Gy). AC-based regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF).

Results

Concomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4 toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value. Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients.

Conclusions

In our experience, concomitant chemotherapy did not emerge as a significant factor in radiotherapy interruption. Moreover, no severe cardiac events were recorded.     

Prolonged survival when temozolomide is added to accelerated radiotherapy for glioblastoma multiforme

Background

The goal of this study was to evaluate accelerated radiotherapy with and without temozolomide (TMZ) for glioblastoma multiforme (GBM).

Methods

This retrospective analysis evaluated 86 patients with histologically proven GBM who were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was 90. A total of 41 patients received radiotherapy only from 2002?C2005 and 45 patients were treated with TMZ concomitantly and after radiotherapy from 2005?C2007.

Results

Median overall survival (OS) was 12.5 months and 2-year OS was 15.4%. Patient characteristics were well balanced between the two groups except for better performance status (p = 0.05) and higher frequency of retreatment for the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and treatment with TMZ (HR 0.60) were correlated with OS in the multivariate analysis: treatment with and without TMZ resulted in median OS of 16 months and 11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45 patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant TMZ.

Conclusion

TMZ added to accelerated radiotherapy for GBM resulted in prolonged overall survival with low rates of severe hematological toxicity.     

Moderately hypofractionated radiotherapy for localized prostate cancer

Purpose

To evaluate long-term outcome after dose-escalated, moderately hypofractionated radiotherapy for prostate cancer.

Methods

Since 2005, 150 consecutive patients were treated with primary radiotherapy for localized prostate cancer. Intensity modulated radiotherapy (IMRT) using the simultaneous integrated boost (SIB) technique was practiced in all patients and doses of 73.9 Gy (n?=?41) and 76.2 Gy (n?=?109) were delivered in 32 and 33 fractions, respectively. The pelvic lymph nodes were treated in 41 high-risk patients. Treatment was delivered using cone-beam CT based image-guided radiotherapy (IGRT). Toxicity was assessed prospectively using CTCAE 3.0; biochemical failure was defined according to the Phoenix definition of nadir +?2 ng/ml.

Results

Median follow-up of living patients was 50 months. Gastrointestinal (GI) toxicity was mild with >?80?% of the patients free from any GI toxicity during follow-up and no time trend to increased rates or to higher grade of GI toxicity. Two patients suffered from late grade 3 GI toxicity. Acute genitourinary (GU) toxicity grade 1–2 was observed in 85?% of the patients; most patients recovered quickly within 6 weeks after treatment. The rate of GU toxicity grade ≥?2 was <?10?% at 6–12 month but increased continuously to 22.4?% at 60 months; grade 3 GU toxicity remained below 5?% during follow-up. The 5-year freedom from biochemical failure (FFBF) was 82?% for all patients and 88, 80, and 78?% for low-, intermediate-, and high-risk disease.

Conclusion

Favorable FFBF with simultaneously low rates of toxicity was observed after moderately hypofractionated radiotherapy with 2 Gy-equivalent doses ≥?80 Gy. Conformal IMRT planning and accurate IGRT treatment delivery may have contributed to these results.     

Radiotherapy with or without chemotherapy in the treatment of anal cancer: 20-year experience from a single institute

Purpose

To report the efficacy and toxicity of radio(chemo)therapy (RCT) in the management of squamous cell anal carcinoma (SQ-AC) and to evaluate the prognostic factors influencing the outcomes.

Patients and methods

A consecutive cohort of 138 patients with cT1-4, cN0-3, cM0 SQ-AC were treated with RCT between 1988 and 2011 at our department. Median follow-up time for surviving patients from the start of RCT was 98 months (range, 1–236 months). Patients were treated with a median radiation dose of 56 Gy (range, 4–61 Gy). Concurrent chemotherapy was administered to 119 patients (86%).

Results

The survival rates at 2, 5, and 10 years were 88?±?3, 82?±?4, and 59?±?6%, respectively, with a median overall survival (OS) of 167 months. The cumulative incidence for local recurrence at 2 and 5 years was 8?±?2 and 11?±?3%, respectively. The median disease-free survival (DFS) and colostomy-free survival (CFS) times were 132 and 135 months, respectively. In 19 patients (14%), a distant metastasis was diagnosed after a median time of 19 months. In the multivariate analysis, UICC (International Union Against Cancer) stage I-II, female gender, Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and good/moderate histologic differentiation (G1–2) were significantly associated with a better OS, DFS, and CFS. Conformal radiotherapy planning techniques were significantly associated with a lower cumulative incidence of local recurrence (11?±?3% vs. 38?±?19% at 5 years, p?=?0.006). A higher radiation dose beyond 54 Gy was not associated with an improvement in outcome, neither for smaller—(T1/T2) nor for larger tumors (T3/T4).

Conclusion

RCT leads to excellent outcomes—especially in patients with stage I/II and G1/G2 tumors—with acceptable toxicity. The probable advantages of high-dose radiotherapy should be considered carefully against the risk of a higher rate of toxicity. Future studies are needed to investigate the role of a more intensified (systemic) treatment for patients with unfavorable prognostic factors such as T3/T4, N+, and/or poor cell differentiation.     

Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with 90Y-labeled biotin

Purpose

External beam radiotherapy (EBRT) after conservative surgery for early breast cancer requires 5–7 weeks. For elderly patients and those distant from an RT center, attending for EBRT may be difficult or impossible. We investigated local toxicity, cosmetic outcomes, and quality of life in a new breast irradiation technique—intraoperative avidination for radionuclide therapy (IART)—in which avidin is administered to the tumor bed and ⁹⁰Y-labelled biotin later administered intravenously to bind the avidin and provide irradiation. Reduced duration EBRT (40 Gy) is given subsequently.

Methods

After surgery, 50 (ten patients), 100 (15 patients) or 150 mg (ten patients) of avidin was injected into the tumor bed. After 12-24 h, 3.7 GBq ⁹⁰Y-biotin (beta source for therapeutic effect) plus 185 MBq ¹¹¹In-biotin (gamma source for imaging and dosimetry) was infused slowly. Whole-body scintigraphy and SPECT/CT images were taken for up to 30 h. Shortened EBRT started 4 weeks later. Local toxicity was assessed by RTOG scale; quality of life was assessed by EORTC QOL-30.

Results

Of 35 patients recruited (mean age 63 years; range 42–74) 32 received IART plus EBRT. 100 mg avidin provided 19.5?±?4.0 Gy to the tumor bed and was considered the optimum dose. No side-effects of avidin or ⁹⁰Y-biotin occurred, with no hematological or local toxicity. Local G3 toxicity occurred in 3/32 patients during EBRT. IART plus EBRT was well accepted, with good cosmetic outcomes and maintained quality of life.

Conclusions

IART plus reduced EBRT can accelerate irradiation after conservative breast surgery.     

Phase-II-Studie zur präoperativen Radio-Chemo-Thermo-Therapie beim lokal fortgeschrittenen Rektum-Karzinom

Background

Recent studies show that preoperative radio-chemotherapy can increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia together with radio-chemotherapy in a phase-II study on locally advanced rectal carcinomas.

Patients and Methods

Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preoperative radio-chemo-thermo-therapy. The initial tumor depth was determined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 × 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m²) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regional hyperthermia each week prior to radiotherapy and simultaneously with chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bladder and vagina. Following endosonographic restaging, the operation was carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed.

Results

Thirty-one of the 37 patients (84%) with primary carcinoma proved locally R0-resectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction of depth infiltration from the initial endosonographic stage during preoperative therapy. The actuarial, survival rate after 4 years is 65% (free of progression 57%). The actuarial 4-year survival rate was particularly favorable for the group of responders. Overall, the preoperative multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intestine and skin were reduced as far as possible by field blockings and cooling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperature distribution (T₉₀, cum min T₉₀≥40.5 °C) depends on the power level and relative power density. The response (reduction of tumor size or depth infiltration) correlated significantly with quality parameters of the temperature distributions. This dependency is found as a trend for progression-free survival, too.

Conclusions

Preoperative radio-chemo-thermo-therapy proved to be practical and effective, with encouraging remission rates and excellent local control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical improvements are still under development for regional hyperthermia.     

Dosimetric study of CO-60 source step size in uterine cervix intracavitary HDR brachytherapy

Purpose

The present work reports effects of source step sizes on dose distribution in patients treated with cobalt-60 (Co-60) high-dose-rate afterloading brachytherapy in carcinoma cervix (Ca-cx).

Locally advanced verrucous carcinoma of the oral cavity

Background

Oral verrucous carcinomas are locally invasive but rarely metastasize. Current treatment options include surgery and external beam radiotherapy (EBRT). In medical inoperable patients or irresectable tumors, high-dose-rate (HDR) brachytherapy is a valid alternative.

Case

We present an 85-year-old man with functionally irresectable cT3N0M0 verrucous carcinoma superficially spreading along the upper alveolar ridge to the retro-alveolar triangle, with infiltration of the left soft and hard palate and buccal mucosa. Using a customized intraoral mold, this patient was treated with HDR brachytherapy delivering a dose of 48 Gy in 12 fractions three times per week. Treatment was well tolerated, and after prolonged confluent mucositis the tumor is in complete remission.

Review of literature and conclusion

The scarce literature on customized mold HDR brachytherapy in maxillary tumors is reviewed and recommendations for other head and neck tumors are given.     

Effect of a combined surgery, re-irradiation and hyperthermia therapy on local control rate in radio-induced angiosarcoma of the chest wall

Purpose

Radiation-induced angiosarcoma (RAS) of the chest wall/breast has a poor prognosis due to the high percentage of local failures. The efficacy and side effects of re-irradiation plus hyperthermia (reRT + HT) treatment alone or in combination with surgery were assessed in RAS patients.

Patients and methods

RAS was diagnosed in 23 breast cancer patients and 1 patient with melanoma. These patients had previously undergone breast conserving therapy (BCT, n?=?18), mastectomy with irradiation (n=5) or axillary lymph node dissection with irradiation (n?=?1). Treatment consisted of surgery followed by reRT + HT (n?=?8), reRT + HT followed by surgery (n?=?3) or reRT + HT alone (n?=?13). Patients received a mean radiation dose of 35 Gy (32–54 Gy) and 3–6 hyperthermia treatments (mean 4). Hyperthermia was given once or twice a week following radiotherapy (RT).

Results

The median latency interval between previous radiation and diagnosis of RAS was 106 months (range 45–212 months). Following reRT + HT, the complete response (CR) rate was 56?%. In the subgroup of patients receiving surgery, the 3-month, 1- and 3-year actuarial local control (LC) rates were 91, 46 and 46?%, respectively. In the subgroup of patients without surgery, the rates were 54, 32 and 22?%, respectively. Late grade 4 RT toxicity was seen in 2 patients.

Conclusion

The present study shows that reRT + HT treatment—either alone or combined with surgery—improves LC rates in patients with RAS.     

Famotidine as a radioprotector for rectal mucosa in prostate cancer patients treated with radiotherapy

Background and purpose

Acute bowel toxicity significantly affects the quality of life of patients treated with pelvic radiotherapy. This study was performed to assess whether pretreatment with famotidine can reduce acute radiation toxicities in patients undergoing radiotherapy for prostate cancer.

Patients and methods

Between April 2012 and February 2013, 36 patients undergoing radiotherapy for prostate cancer were enrolled to receive either placebo or famotidine. The patients received external-beam radiotherapy up to 70 Gy at daily fractions of 1.8–2 Gy (5 days/week). Oral famotidine 40 mg (80 mg/day) or placebo was administered twice daily (4 and 3 h prior to each radiotherapy fraction). Bowel and bladder acute toxicities were evaluated weekly during radiotherapy and once thereafter according to RTOG grading criteria.

Results

Famotidine was well tolerated. No grade III or higher acute toxicities were noted in the two groups. Grade II rectal toxicity developed significantly more often in patients receiving placebo than in patients receiving famotidine (10/18 vs. 2/16, p?=?0.009). Moreover, no rectal bleeding occurred in the famotidine group, while 5 patients in the placebo group experienced rectal bleeding during treatment (p?=?0.046). The duration of rectal toxicity in the radiotherapy course was also reduced in the famotidine group (15.7 vs. 25.2 days, p?=?0.027). No significant difference between the two groups was observed in terms of urinary toxicity.

Conclusion

We demonstrated for the first time that famotidine significantly reduces radiation-induced injury on rectal mucosa representing a suitable radioprotector for patients treated with radiotherapy for prostate cancer.     

Outcomes of freehand interstitial brachytherapy in advanced gynecologic malignancies

PurposeThe purpose of the study is to present the first results of freehand interstitial brachytherapy (ISBT) used to treat patients with carcinoma of the cervix and the vagina.Methods and MaterialsPatients diagnosed with carcinoma of the cervix or carcinoma of the vagina who were not suitable for intracavitary brachytherapy were treated with freehand ISBT. The implant was performed transperineally using C arm or transrectal ultrasound guidance. Patients received an external beam radiotherapy dose of 50 Gy in 25 fractions. The dose delivered by high-dose-rate ISBT was 18 Gy in three fractions, 6 Gy per fraction, 6 h apart. The brachytherapy dose volume parameters were analyzed after CT-based planning using GEC ESTRO image-guided brachytherapy-based guidelines.ResultsFrom June 2018 till November 2018, 14 patients were treated with freehand ISBT. The mean dose received by 90% of the high-risk clinical target volume (D₉₀) was 82 Gy EQD2₁₀ for patients with carcinoma of the cervix and 80 Gy EQD2₁₀ for patients with carcinoma of the vagina_. The mean dose received by 2 cc volume of the bladder and rectum was 80 Gy EQD2₃ and 70 Gy EQD2₃ for patients with carcinoma of the cervix and 75 Gy EQD2₃ and 72 Gy EQD2₃ for patients with carcinoma of the vagina, respectively. The mean dose received by 2 cc of the sigmoid was 65 Gy EQD2₃ for cervical carcinoma and 58 Gy EQD2₃ for vaginal carcinoma, respectively. At a median followup of 14 months, 2 patients developed local recurrence. Two patients developed Grade 2 gastro intestinal toxicity, and 1 patient developed Grade 2 genitourinary toxicity. None of the patients developed Grade 3 or 4 toxicities.ConclusionA freehand interstitial implant is feasible in resource limited settings and provides acceptable local control with minimal acute toxicity.     

Benefit of replacing the Sigma-60 by the Sigma-Eye applicator

Background and purpose

To investigate the clinical benefit of replacing the BSD-2000 Sigma-60 with the Sigma-Eye applicator, taking into account effects of uncertainties in tissue and water bolus parameters.

Patients and methods

For 20 patients, specific absorption rate (SAR) and temperature distributions were calculated and optimized, based on computed tomography (CT) scans in treatment position. The impact of uncertainties on predicted distributions was studied using a Monte Carlo uncertainty assessment.

Results

Replacing the Sigma-60 by the Sigma-Eye applicator resulted in a higher SAR in the tumor [on average a decrease of the hotspot tumor quotient (HTQ) by 24%; p?<?0.001], and higher temperatures (T90: +0.4°C, p?<?0.001; T50: +0.6°C, p?<?0.001) using literature values and SAR optimization. When temperature optimization (T90) was used, a larger average increase was found (T90: +0.7°C, p?<?0.001; T50: +0.8°C, p?<?0.001). When taking into account uncertainties, a decrease of 23% in median HTQ (p?<?0.001) and an increase in T50 and T90 of 0.4°C (p?<?0.001) could be demonstrated.

Conclusion

Based on this uncertainty analysis, significant and clinically relevant improvements in HTQ and tumor temperature were achieved when replacing the Sigma-60 by the Sigma-Eye applicator.