Initial External Beam Radiotherapy Research Articles

Brachytherapy in gynecological malignancies at a tertiary care hospital: An analysis.

Brachytherapy plays a crucial role in the standard of care for locally advanced gynecological malignancies. In this report, we present the experience from a tertiary teaching hospital, which is a referral center for image-guided brachytherapy (IGBT) in the management of locally advanced gynecological malignancies. This was a retrospective study of 130 patients referred to our hospital for IGBT after receiving initial external beam radiotherapy in their primary healthcare facilities, from January 2021 till January 2023. CT-based planning was done to delineate high-risk clinical target volume (HR-CTV). Dose of 6-7.5 Gy in 3-4 fractions was prescribed. Overall treatment time (OTT) was calculated, and patients were assessed for clinical response and toxicity after three months. All patients received IGBT using an intra-cavitary or interstitial technique. The D90 HR-CTV mean EQD2 dose was 28.34 ±2.78 Gy. The mean EQD2 dose to 2 cc of the bladder, rectum, and sigmoid was 18.31 ±5.19 Gy, 14.14 ±5.76 Gy, and 17.43 ±4.75 Gy, respectively. The median interval time between the last fraction of external beam radiation therapy (EBRT) and first evaluation in the hospital was 19 (range, 13-28) days (interquartile range [IQR]). The median time between the completion of chemoradiation and brachytherapy procedure was 25 (range, 19-33) days (IQR). The mean overall treatment time (OTT) was 63.5 ±14.7 days. This study highlights the established advantages of image-guided interstitial brachytherapy and associated challenges. To optimize the overall treatment duration, it is imperative to prioritize and update the referral processes for brachytherapy centers.

Novel combination of GammaTile cesium-131 brachytherapy with 5-aminolevulinic acid fluorescence-guided resection in the re-irradiation of pediatric recurrent high-grade glioma: illustrative case.

Herein, the authors describe the successful utilization of 5-aminolevulinic acid (5-ALA) and the first case of GammaTile cesium-131 therapy in a pediatric patient with recurrent high-grade glioma. 5-ALA was utilized to optimize gross-total resection prior to GammaTile implantation. After conversion to an equivalent dose in 2-Gy fractions (EQD2), a composite was made of the GammaTile dose with the initial external beam radiotherapy. Two hypothetical plans consisting of a standard hypofractionated strategy for glioma reirradiation and a CyberKnife plan using GammaTile's planning target volume were developed and likewise underwent EQD2 conversion and composite plan generation with the initial radiotherapy. 5-ALA was useful in achieving gross-total resection with no acute toxicity from the surgery or GammaTile irradiation. When compared with the hypothetical composite doses, GammaTile's composite, axium point dose (D0.03cc) to the brainstem was 32.9 Gy less than the hypofractionated and the CyberKnife composite plans at 38.7 Gy and 40.2 Gy, respectively. The right hippocampus demonstrated a substantially reduced composite plan dose with GammaTile with a D0.03cc of 62.4 Gy versus 71.7 and 80.7 Gy for the hypofractionated and CyberKnife composite plans, respectively. Utilization of 5-ALA and GammaTile therapy yielded clinically superior tumor debulking and effective radiotherapy dose localization with sparing of organs at risk, respectively.

Salvage focal brachytherapy in castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy.

IntroductionTreatment strategy for castration‐resistant prostate cancer with neuroendocrine differentiation after radiation therapy has not been established.Case presentationWe described a case of castration‐resistant prostate cancer with neuroendocrine differentiation after initial external beam radiotherapy followed by salvage androgen deprivation therapy. Magnetic resonance imaging detected recurrence of a suspicious lesion in the left lobe of the prostate, although the prostate‐specific antigen level was <0.2 ng/mL. Transperineal prostate saturation needle biopsy detected adenocarcinoma with neuroendocrine differentiation. The patient underwent salvage focal brachytherapy and had a prostate‐specific antigen progression‐free survival of 20 months with no obvious adverse events. No recurrence has been detected on magnetic resonance imaging for 18 months.ConclusionSalvage focal brachytherapy for prostate cancer after external beam radiotherapy can be one of the treatment strategies for local recurrence of castration‐resistant prostate cancer with neuroendocrine differentiation.

Intraprostatic Abscess as a Complication of Salvage Cryotherapy

We present a case of prostatic abscess as a previously unreported complication of salvage cryoablation after initial external beam radiotherapy for prostate cancer. An 81-years-old gentleman presented with recurrent urinary tract infection, unresolved after repeated antibiotic treatments, and severe abdominal, back, and perineal pain that developed 2 weeks after undergoing cryotherapy at an outside institution. The patient required open operative drainage of 6 cm prostatic abscess-like cavity noted on computed tomography pelvis and long-term outpatient intravenous antibiotics. This is the first published instance of cryoablation therapy associated with prostatic abscess.

Adjuvant hysterectomy following unsuccessful intracavitary brachytherapy in cervical carcinoma

e16543 Background: In cervical carcinoma unsuccessful intracavitary brachytherapy (ICBT) treatment results in sub-optimal chemoradiation (CRT) thus increasing risk of recurrence. Optimal management following unsuccessful ICBT remains undefined. Methods: Retrospective analysis of all women with cervical carcinoma treated from January 2000-July 2007 where ICBT insertion was unsuccessful following initial pelvic external beam radiotherapy (EBRT). Data collected and analysed included histology, stage of disease, response to initial CRT, cause for unsuccessful ICBT insertion and subsequent treatment received, morbidity, and recurrence and survival rates. Results: ICBT insertion was unsuccessful in 18 out of 207 (8.7%) women. Causes of failure included: unable to dilate cervix (3); uterine perforation (2); vesicovaginal fistula (2); patient refusal (3); other problems, e.g., pyometrium (4); consultant choice- no obvious reason (4). 13/18 women (72%) received further pelvic EBRT alone. The remaining 5 women (28%) underwent adjuvant hysterectomy, all within 21 days of completing EBRT. 12/18 women (66%) remain alive and recurrence-free at a median follow-up of 6 years. 6/13 women (46%) in the EBRT alone group have died of disease recurrence of which only 1 patient did not develop pelvic relapse. 3/6 patients had potentially resectable disease at examination under anaesthesia (EUA) prior to attempted ICBT insertion with subsequent MRI scanning demonstrating an apparent near complete initial radiological response. Another patient with initial FIGO stage 2A cervical carcinoma absconded from treatment and potentially had resectable disease following initial CRT. The remaining 2 patients had unresectable disease at EUA. All 5 women in the adjuvant hysterectomy group remain alive and recurrence-free with no patient developing any significant late toxicity such as bowel stenosis or fistula. Conclusions: Adjuvant hysterectomy following unsuccessful ICBT does not appear to increase late toxicity and reduces risk of pelvic recurrence. This may be considered as a treatment option for any woman having sub-optimal CRT where the residual tumour remains operable after initial EBRT. No significant financial relationships to disclose.

Clinical Impact of Computed Tomography-based Image-guided Brachytherapy for Cervix Cancer using the Tandem-ring Applicator — the Addenbrooke's Experience

Aims We report our initial 3-year experience of chemoradiotherapy for cervical cancer with computed tomography-based image-guided high dose rate (HDR) brachytherapy using the tandem-ring applicator. Materials and methods Twenty-eight patients were treated between February 2005 and December 2007. All patients received initial external beam radiotherapy (EBRT) followed by HDR brachytherapy (planned dose 21 Gy to point A in three fractions over 8 days). For each insertion, a computed tomography scan was obtained with the brachytherapy applicator in situ. The cervix, uterus and organs at risk (OAR) were contoured on the computed tomography images to create an individualised dosimetry plan. The D 90 (the dose delivered to 90% of the tumour target), V 100 (the percentage of tumour target volume receiving 100% of the prescribed dose) and the minimum dose in the most exposed 2 cm 3 volume ( D 2cc) of rectum, bladder and bowel were recorded. The equivalent dose in 2 Gy fractions delivered by EBRT and brachytherapy was calculated. Results The 3-year cancer-specific survival was 81%, with a pelvic control rate of 96%. In 24 patients, a D 90 ≥74 Gy α/β10 was achieved. The only patient with local recurrence had a D 90 of 63.8 Gy α/β10. The overall actuarial risk of serious late morbidity was 14%. Seventeen patients had satisfactory OAR doses using the standard loading pattern. Seven patients had modifications to reduce the risk of toxicity, whereas two had modifications to improve the tumour dose. Comparison with a previous cohort of patients treated with chemoradiotherapy and a conventionally planned low dose rate triple source brachytherapy technique showed an improvement in local pelvic control of 20% ( P = 0.04). Conclusions The implementation of a computed tomography-based tandem-ring HDR brachytherapy technique in conjunction with individual dose adaptation has resulted in a significant improvement in local control at Addenbrooke's without increasing the risk of serious toxicity, and with little effect on radiotherapy resources.

Hypofractionated stereotactic radiotherapy combined with topotecan in recurrent malignant glioma

Purpose: To assess hypofractionated stereotactic radiotherapy (H-SRT) with concurrent topotecan in patients with recurrent malignant glioma. Methods and Materials: Between February 1998 and December 2001, 25 patients with recurrent malignant glioma were treated in a phase I-II study (8 females and 17 males; median age, 45 years; range, 11–66 years; median Karnofsky performance status, 80%, range, 50–100%; median Mini Mental Standard Examination score, 25 points; range, 10–30 points). Of the 25 patients, 20% had World Health Organization Grade III and 80% World Health Organization Grade IV glioma. All patients had been treated previously by external beam radiotherapy with 54.4 Gy in 34 fractions twice daily, at least 6 h apart, within 3.5 weeks or 60 Gy in 30 fractions within 6 weeks. In addition, 84% had already received at least one chemotherapy regimen for recurrence. The median H-SRT dose at the 80% isodose was 25 Gy, and the maximal dose was 30 Gy delivered in five to six fractions on consecutive days. Topotecan (1.1 mg/m 2 /d) was given as a continuous i.v. infusion during H-SRT. Depending on the toxicity and compliance, patients received an additional 48 topotecan courses. Results: For all patients, the actuarial median progression-free survival was 10.5 months (range, 1.4–47.8 months), the median functional survival was 12.6 months (range, 1.6–49.5 months), and the median overall survival was 14.5 months (range, 3–56.4 months). Twelve percent of patients developed presumed adverse radiation effects (Radiation Therapy Oncology Group Grade 2). According to the Common Toxicity Criteria, version 2.0, no topotecan-related Grade 4 toxicity was noted. Grade 3 neutropenia was documented after 14 and Grade 3 thrombopenia after 12 courses. Conclusion: H-SRT with topotecan is feasible and well-tolerated in patients with recurrent high-grade glioma and results in similar survival compared with other repeat treatment modalities.

Outcome Following Initial External Beam Radiotherapy in Patients With Reese-Ellsworth Group Vb Retinoblastoma

Outcome Following Initial External Beam Radiotherapy in Patients With Reese-Ellsworth Group Vb Retinoblastoma

HIV impact on acute morbidity and pelvic tumor control following radiotherapy for cervical cancer

Objective. To determine the impact of HIV infection on acute morbidity and pelvic tumor control following external beam radiotherapy (EBRT) for cervical cancer. Method. 218 patients receiving EBRT who also had HIV testing after informed consent was obtained were evaluated. Acute treatment toxicity was documented weekly during treatment and 1 month post-EBRT. Pelvic tumor control was documented at 4 and 7 months post-EBRT. Clinicians were blinded for HIV results. Results. About 20% of the patients were HIV-positive. Overall, 53.4% of the patients had radiation-related acute toxicity (grade 3–4). HIV infection was associated with a 7-fold higher risk of multisystem toxicity: skin, gastrointestinal tract (GIT) and genitourinary tract (GUT) systems. It was also an independent risk factor for treatment interruptions (adjusted relative risk 2.2). About 19% of the patients had residual tumor at 4 and 7 months post-EBRT. HIV infection was independently and significantly associated with 6-fold higher risk of residual tumor post-EBRT. The hazard ratio of having residual tumor after initial EBRT was 3.1-times larger for HIV-positive than for HIV-negative patients ( P = 0.014). Conclusion. HIV is associated with increased risk of multisystem radiation-related toxicity; treatment interruptions and pelvic failure (residual tumor) following EBRT. HIV infection is an adverse prognostic factor for outcome of cervical cancer treatment.

Outcome following initial external beam radiotherapy in patients with Reese-Ellsworth group Vb retinoblastoma.

To describe patient and ocular outcomes following initial treatment with external beam radiotherapy (EBT) in eyes with Reese-Ellsworth group Vb retinoblastoma. Retrospective case series (from January 1, 1979, to February 28, 2002). The Kaplan-Meier method was used to analyze survival (ocular and patient) and incidence (second cancer) data. Two hundred forty-three patients with 1 or more Reese-Ellsworth group Vb eyes were identified. Of 284 group Vb eyes, 63 (22.2%) initially received EBT, vs 172 (60.6%) that were initially enucleated. Of the 63 radiated group Vb eyes, 31 (49.2%) had no further tumor growth, 26 (41.3%) developed a recurrence, and 8 (12.7%) developed a new tumor. Of the 63 radiated group Vb eyes, 33 (52.4%) developed ocular complications. The ocular survival rate of radiated group Vb eyes was 81.4% at 1 year and 53.4% at 10 years. Twenty-eight radiated group Vb eyes survived to the last follow-up with visual acuity information. Thirteen patients developed second cancers, 11 in the field of radiation. The probability of developing a second cancer following initial EBT for group Vb disease in patients with bilateral disease was 29.7% by 10 years after diagnosis. Survival from second cancers in patients with bilateral disease initially receiving EBT for group Vb disease was 93.6% at 5 years and 52.6% at 18(1/4) years. No patient with unilateral disease developed a second cancer. Deaths due to metastatic retinoblastoma were uncommon. To our knowledge, this is the first study focusing exclusively on group Vb eyes treated initially with EBT, most of which were salvaged with vision. Outcome data provided herein are clinically relevant when choosing treatment options for advanced intraocular retinoblastoma.

LOCAL TUMOR CONTROL WITH SALVAGE CRYOTHERAPY FOR LOCALLY RECURRENT PROSTATE CANCER AFTER EXTERNAL BEAM RADIOTHERAPY

We identified variables associated with a positive prostate biopsy after salvage cryotherapy in patients in whom initial external beam radiotherapy for prostate cancer failed to improve our cryotherapy technique, optimize local control and improve our patient selection criteria for salvage cryotherapy. Between July 1992 and January 1995, 145 patients underwent salvage cryotherapy. Post-cryotherapy sextant prostate biopsies were performed in 107 cases. We evaluated certain variables on univariate and multivariate analysis as predictors of a positive biopsy after cryotherapy, including the type of previous therapy, tumor stage and grade at initial diagnosis, prostate volume, pre-cryotherapy prostate specific antigen (PSA), number of positive biopsy cores before cryotherapy, PSA nadir after cryotherapy, stage and grade of local recurrence, number of cryoprobes, number of freeze-thaw cycles and use of a urethral warming catheter during cryotherapy. Biopsies were positive in 23 cases (21%) after salvage cryotherapy. Variables associated with a positive biopsy on univariate analysis were initial stage, precryotherapy PSA, PSA nadir after cryotherapy, number of cryoprobes, number of freeze-thaw cycles and a history of chemotherapy (p = 0.005, 0.027, 0.001, 0.009, 0.018 and 0.008, respectively). Variables that remained associated with a positive biopsy on multivariate analysis were the number of probes used and post-cryotherapy PSA nadir (p = 0.013 and 0.019, respectively). Patients with initial clinical stage T1-2N0M0 disease and PSA no more than 10 ng./ml. have a higher rate of negative biopsies after salvage cryotherapy. Therefore, they are better candidates for salvage cryotherapy for locally recurrent prostate adenocarcinoma after external beam radiotherapy. To optimize the potential for local control the technique of salvage cryotherapy should include 2 freeze-thaw cycles and a minimum of 5 cryoprobes. Detectable PSA after salvage cryotherapy is a strong predictor of local failure.

Brachytherapy

I read with great interest the article by Koot et al.1 comparing the results of two completely different concepts of interstitial brachytherapy in the treatment of patients with glioblastoma multiforme (GBM). The regimens differ with regard to the extent of initial surgery (biopsy vs. cytoreductive surgery), the isotope used (iodine-125 vs. iridium-192), the dose given via external beam radiotherapy (EBRT) (10–30 grays [Gy] vs. 60 Gy), the brachytherapy target volume (contrast-enhancing region without margin vs. that with a 5-mm margin), and the timing of the treatment (initial brachytherapy with simultaneous EBRT vs. initial EBRT followed by interstitial boost). Despite these contrasting concepts, a median survival of 17 months and 16 months, respectively, was observed in defined subgroups (those age > 30 years with a Karnofsky performance score ≥ 70 and a nonmidline tumor) from both cohorts compared with a median survival of 10 months in a control group. Unfortunately, the authors missed an opportunity to shed more light on a central, unresolved issue concerning radiation therapy for GBM: the criteria defining the volume to be treated with higher-than-conventional doses. First, the report by Koot et al. lacks information concerning how the brachytherapy planning target volume (PTV) was defined. Apparently, the PTV definition was based on contrast enhancement on computed tomography (CT), and in some cases magnetic resonance imaging (MRI) was used instead or as additional information. Taking into account that these two imaging modalities already differ substantially in outlining malignant gliomas,2 it is essential to know how CT and MRI contributed to the PTV definition (combined volume or an overlap of both methods?). In addition, there was no information at all presented with regard to the definition of EBRT volumes and the imaging and criteria used to define disease progression. The authors only state that in the 1 cohort, 51% of the patients recurred “outside the margins of the isodose distribution” (the prescription isodose?) and that in the other group, all recurrences occured “at the original site” (inside the brachytherapy PTV or inside the EBRT PTV?). Interstitial brachytherapy in the treatment of GBM competes with noninvasive modalities such as high-dose proton/photon radiotherapy3 and stereotactic EBRT boost after conventional radiotherapy, with the latter currently being studied in what to my knowledge are ongoing randomized trials.4, 5 Both concepts have demonstrated comparable, although mixed, results in Phase II studies, with estimated survival advantages of 5–11 months compared with conventional treatment.4, 6 In contrast to the report by Koot et al.,1 these studies presented a thorough analysis of patterns of recurrence, demonstrating a true shift from the common central recurrence after conventional radiotherapy7 to marginal recurrence after central high-dose treatment. For example, Fitzek et al. observed histologically confirmed recurrent tumor within the high-dose volume in only 1 case despite a high reoperation rate of 57% in a group of 23 GBM patients treated with 90 cobalt gray equivalent with proton/photon irradiation.3 In contrast, new MRI enhancement after treatment within that same volume was found in 78% of patients, underscoring the difficulty in differentiating between necrosis and tumor recurrence. In a series of 78 GBM patients treated with a stereotactic EBRT boost, Shrieve et al. found only 38% of recurrences developed within 2 cm of the boost prescription isodose.6 To interpret the results of the study by Koot et al.,1 it would be helpful to know exactly where the recurrences (defined by imaging or pathology at reoperation) occured with regard to PTV or treated volume. If there is any benefit to high-dose radiotherapy by any method in the treatment of GBM, it lies in the treatment's ability to sterilize the central region of the solid tumor. Although this potential benefit must be weighed carefully against the risk of radiation-induced necrosis, several investigators have called for an extension of the high-dose target volume beyond the area of contrast enhancement.3, 8 The definition of such extended volumes may include additional information regarding tumor outline using modalities such as single photon computed emission tomography9 or transcranial sonography.10 In any case, the treatment of GBM patients beyond conventional radiotherapy doses and a potential optimization of current concepts calls for a clear definition of the target volumes used and a particularly thorough documentation of the patterns of tumor recurrence. [The authors were invited to reply and declined the invitation.] Dirk Vordermark M.D.*, * Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany

Retreatment of patients with intracranial gliomas by external beam radiotherapy and cytotoxic chemotherapy

Twenty-one patients with recurrent intracranial gliomas were retreated by external beam radiotherapy between 1987 and 1995. Twenty patients received cytotoxic chemotherapy involving CCNU as part of their retreatment. Only five of the 21 patients had received chemotherapy in combination with the initial external beam radiotherapy (RT) prior to recurrence. The different histological groups were analysed and the patients divided into two groups; group I (Grade I and II gliomas) and group II (Grade III, IV and glioblastoma). The overall median survival for all patients was 59 months, with a median survival of 22 months after recurrence. For group I and group II patients, the median survival was 26 months and 13 months after recurrence respectively. It was concluded that some highly selected patients with intracranial gliomas can be retreated safely by carefully planned external beam RT given to a relatively low dose in order to palliate neurological dysfunction and the symptoms of raised intracranial pressure, and to reduce steroid dependency. The results strongly suggest that recovery does occur after initial RT. Retreatment may possibly improve survival in a small proportion of patients. Further studies, including randomized trial designs, quality of life assessment, and neurological symptoms indices, would be required to determine the quantitative benefit of any such treatment policy. The objectives of this study were to determine whether patients received any benefit, such as symptom relief and the allowance of steroid withdrawal, after retreatment, and whether long term survival could be achieved.

Treatment of carcinomas of the uterine cervix which remain bulky after initial external beam radiotherapy: a pilot study using integrated cytotoxic chemotherapy prior to brachytherapy.

The use of cytotoxic chemotherapy (CT) between external beam radiotherapy (EBRT) and intracavitary brachytherapy (BT) in patients with bulky carcinomas of the uterine cervix which regress poorly after initial EBRT has been evaluated in a pilot study. The aim of CT was to limit tumour clonogen repopulation while awaiting further tumour regression in order to improve the BT dose distribution. Between 1989 and 1992, 22 patients with FIGO Stage IIA, IIB and IIIB cervical carcinomas were given two to three cycles of cisplatin-based CT between EBRT and intracavitary BT. Patients were selected for CT if there was bulky residual tumour extending beyond the range of point "A" after completion of EBRT. The median survival of patients with Stage IIA/B and Stage IIIB disease was 24 months and 13 months, respectively. The 5 year actuarial survival rate for patients with Stage IIA/B disease was 42%. There were no long-term survivors among patients with Stage IIIB disease. Survival difference between Stage IIA/B patients and Stage IIIB patients was statistically significant (p < 0.04). 5 year actuarial pelvic control rates were 38% and 0% for Stage IIA/B and Stage IIIB patients, respectively. There were no serious late radiation complications in the entire study group. Bulky carcinomas of the cervix which respond poorly to initial EBRT have a particularly poor prognosis. For Stage IB-IIB patients with persistent bulky disease after EBRT, published reports suggest that a 5 year actuarial survival rate of around 40% can be obtained using higher doses of radiation alone, but the risk of serious late morbidity is considerable. The results of our study suggest that in Stage IIA/B carcinomas of the cervix which remain bulky after initial EBRT, the use of integrated cytotoxic chemotherapy prior to intracavitary BT can give similar 5 year survival rates but with minimal treatment related morbidity.