Is hemi-gland focal LDR brachytherapy as effective as whole-gland treatment for unilateral prostate cancer?

PURPOSE: The Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluated hemi-gland (HG) low-dose-rate prostate brachytherapy (LDR-PB) as a focal approach to control unilateral localized prostate cancer and reduce treatment-related toxicity at 2-years postimplant. Herewith we present further outcomes with a minimum of 5 years post-implant follow-up. METHODS AND MATERIALS: Outcomes of 30 HG implants and 362 whole-gland (WG) brachytherapy controls were monitored with IPSS, urinary Quality-of-Life (QoLU), GI component of EORTC-PR25 (QoLB), and IIEF-5 instruments, and PSA values. The median (range) follow-up for HG and WG cases was 72 (60-96) months and 84 (24-144) months respectively. RESULTS: The IPSS was significantly reduced in HG relative to WG patients and trends indicating improved bowel QoL and erectile function were observed. The mean of change in PSA from baseline to last follow-up was -5.6 and -6.5 in HG and WG respectively (p = 0.1). The mean time to nadir was 4.2 and 4.8 years in HG and WG respectively (p = 0.06). Over time PSA in HG patients mirrored the sustained decline observed in WG cases but levels were higher by an average 0.5 ng/ml over WG controls (p < 0.001). Treatment failure occurred in 2 (6.7%) HG patients and in 20 (5.5%) WG cases. Five-year relapse-free survival was 97% in both groups (p = 0.7). CONCLUSIONS: At 5 years postimplant HG LDR-PB was as effective as WG treatment for control of unilateral localized prostate cancer with moderate improvement in treatment-related symptoms. Importantly, PSA is a valuable marker to assess disease control in this form of focal therapy.

Hemi-ablative low-dose-rate prostate brachytherapy for unilateral localised prostate cancer.

OBJECTIVES: To report clinical outcomes of the Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment-related toxicity and effectiveness of hemi-gland (HG) low-dose-rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised prostate cancer. PATIENTS AND METHODS: Single institution phase IIS pilot study of patients treated with focal 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient-reported toxicity 24 months after implant. The secondary outcome was assessment of disease control. Outcomes in HG patients were compared to whole-gland (WG) controls obtained from our prospective cohort registry by negative binomial and linear regression models. RESULTS: Pre-treatment demography was similar between the 30 HG patients and 362 WG controls. Post-implant dosimetry was similar for the prostate gland target volumes and significantly reduced for the urethra and bowel in HG patients relative to WG controls, but this did not translate into a difference in post-implant mean symptom scores between the two groups. Nevertheless, the change in score from baseline indicated that the impact on pre-treatment symptom status was less after HG implants. Only HG patients showed a return to baseline urinary scores as early as 12 months. Sexual potency was conserved in 73% and 67% of HG and WG patients, respectively (P = 0.84). Post-implant prostate-specific antigen (PSA) kinetics revealed that baseline PSA was reduced at 24 months by 78% and 88% in HG and WG patients, respectively (P < 0.05). Treatment relapse occurred in one (3%) HG patient 55 months after implant and in nine (3%) WG patients at 32-67 months after implant. CONCLUSION: This pilot study suggests that treatment-related toxicity and biochemical outcomes after HG implants are broadly similar to those observed with WG treatment despite the lower dose delivered by HG implants.

Perioperative prehabilitation and rehabilitation in esophagogastric malignancies: a systematic review.

Cancers of the esophagus and stomach are challenging to treat. With the advent of neoadjuvant therapies, patients frequently have a preoperative window with potential to optimize their status before major resectional surgery. It is unclear as to whether a prehabilitation or optimization program can affect surgical outcomes. This systematic review appraises the current evidence for prehabilitation and rehabilitation in esophagogastric malignancy. A literature search was performed according to PRISMA guidelines using PubMed, EMBASE, Cochrane Library, Google Scholar, and Scopus. Studies including patients undergoing esophagectomy or gastrectomy were included. Studies reporting on at least one of aerobic capacity, muscle strength, quality of life, morbidity, and mortality were included. Twelve studies were identified for inclusion, comprising a total of 937 patients. There was significant heterogeneity between studies, with a variety of interventions, timelines, and outcome measures reported. Inspiratory muscle training (IMT) consistently showed improvements in functional status preoperatively, with three studies showing improvements in respiratory complications with IMT. Postoperative rehabilitation was associated with improved clinical outcomes. There may be a role for prehabilitation among patients undergoing major resectional surgery in esophagogastric malignancy. A large randomized controlled trial is warranted to investigate this further.

Improving dose delivery by adding interstitial catheters to fixed geometry applicators in high-dose-rate brachytherapy for cervical cancer.

PURPOSE: Image-guided brachytherapy (IGBT) is an essential component of the treatment of locally advanced cervical cancer. Interstitial (IS) catheters are being increasingly used for bulkier tumors. We have retrospectively assessed the dosimetric impact of IS catheters. METHODS AND MATERIALS: All patients who received IGBT for cervical cancer between August 2014 and February 2017 were identified. Clinical and dosimetric data were collected. Patients were grouped into the intracavitary (IC) cohort or the IC and IS implant (IC/IS) cohort. Ten patients who had been treated with IS catheters (IC/IS plan) had their brachytherapy replanned without IS catheters (IC plan). The total D90% received by the high-risk clinical target volume (CTVHR) and the D2cm3 (minimum dose received by the most irradiated 2 cm3) to the bladder, bowel, sigmoid, and rectum were compared. RESULTS: Forty-two patients received IGBT in this period. Seventy-four percent of patients were treated with IS catheters. Sixty-one percent of patients in the IC/IS cohort had CTVHR volumes ≥30 cm3 at Fraction 1 compared to 18% in the IC cohort (p = 0.014). There was no difference in cumulative D90% to CTVHR between the IC/IS cohort and the IC cohort. The replanned brachytherapy showed that the cumulative CTVHRD90% was on average 5.8 Gy higher when IS catheters were used (mean CTVHRD90% 86.1 compared to 80.3 Gy, p < 0.001). The D2cm3 to the organs at risk was not significantly increased. CONCLUSIONS: IS catheters allow the dose to the CTVHR to be escalated significantly without increasing the dose to the bladder, bowel, sigmoid, and rectum in patients with bulky tumors.

Post mortem study of the depth and circumferential location of sympathetic nerves in human renal arteries--implications for renal denervation catheter design.

OBJECTIVES: The aims of this study were to examine human renal arteries and to accurately characterize their sympathetic innervation and location using CD-56 immunohistochemistry stains to highlight Neural Cell Adhesion Molecules (N-CAM). BACKGROUND: Porcine models have often formed the basis for design of denervation technology, with only a limited number of human studies available to detail the complex microarray of renal sympathetic nerves. METHODS: Post-mortem renal arteries (N = 14) were harvested and prepared into three sections (proximal, mid, and distal), and then stained using Hematoxylin and Eosin, followed by immunohistochemistry to characterize the expression of CD-56 renal neural tissue. Digital micro calipers were then used to measure the nerve distances and locations within the vessels. RESULTS: (i) Approximately 77% of nerves are located between 0.5 and 2.5 mm from the tunica intima layer, with 22.5% occurring in the 2.5-5.0 mm range, (ii) nerve bundles occur in 3-dimensional arborized arrays, (iii) the nerve bundles are evenly distributed throughout the proximal and distal vessel in this human study. Thickness of vessel wall correlated with proximity of the nerve bundles (r = 0.74, P < 0.01), and nerve bundle thickness (r = 0.62, P = 0.04). The larger the internal and external diameters and areas of the vessel were, the further the distance to the nearest nerve bundles were (r = 0.752, P =<0.01). CONCLUSIONS: In human renal arteries with larger diameters and thicker vessel parenchyma, the innervation is found further from the lumen, and the nerves increase in thickness. This has implications for catheter and system design, as well as depth and duration of energy required for effective ablations. Effective percutaneous transluminal denervation procedures in this population would need to be circumferential rather than interrupted, and to mediate tissue damage to depths beyond 2.5 mm from the tunica intima.

Single port laparoscopic surgery for patients with complex and recurrent Crohn's disease.

BACKGROUND: Single port laparoscopic surgery (SPLS) is a modified access technique allowing grouping of instruments at a single parietal site. It is intuitively appealing specifically for patients with Crohn's disease (CD) as its minimal invasiveness favors cosmesis and facilitates any future (re)operation. METHODS: Consecutive patients presenting either electively or urgently for resectional surgery for CD over a 36 month period were considered for SPLS using, by preference, a transumbilical 'Surgical Glove Port'. Standard, straight laparoscopic instrumentation was used without additional resources. RESULTS: Of 33 consecutive, unselected patients, 28 (92%) had their procedure initiated by SPLS including those needing urgent intervention (n=15) and those with prior abdominal operation (n=8), obstruction (n=7), mass (n=6), fistula (n=6) and/or abscess (n=4). The median (range) age and BMI of the patients were 31 (17-69) years and 21.3 (18.6-28) kg/m2 respectively. 31 had ileocolonic resection (6 with recurrent disease) while two underwent segmental colectomy. No-one suffered intraoperative or anastomotic complication. Both conversion (15%) and postoperative complication (13 Clavian-Dindo complications - I: 8; II: 2; IIIa: 3) rates were predominantly reflective of patient and disease complexity. Median (range) postoperative day of discharge was 6 (3-33) overall and 5 (3-18) in those completed by SPLS. There was one early readmission (for infectiouscolitis) and median follow-up is now 21 months. CONCLUSIONS: Complex and recurrent Crohn's resections can be performed by SPLS in the majority of patients presenting elective or urgently for surgery. The Surgical Glove Port performs capably and, by minimizing cost, can facilitate broad embrace of this approach.

Correlation between prostate brachytherapy-related urethral stricture and peri-apical urethral dosimetry: a matched case-control study.

BACKGROUND AND PURPOSE: Radiation dose to the bulbomembranous urethra has been shown to correlate with urethral stricture formation. This retrospective case-control study was designed to explore the relationship between dose to the apical/peri-apical regions of the urethra and development of brachytherapy (BXT)-related urethral stricture. MATERIALS AND METHODS: Cases were patients who developed urethral stricture after treatment with BXT as monotherapy and who had urethral dosimetry post-implant. Each case was matched with a control that had not developed urethral stricture. Dosimetry was compared between cases and controls. RESULTS: Twenty-three cases were pair matched with 23 controls. There were no significant differences between the two groups in terms of age, presenting Prostate Specific Antigen (PSA), International Prostate Symptom Score (IPSS) or Gleason score. The dose delivered to the peri-apical and apical urethra was significantly higher for cases when compared with controls (peri-apical urethra: mean V(150) 1.1 Vs 0.8 cc [p=0.02]; apical urethra: mean dose 200 Vs 174 Gy [p=0.01]). The distance from the prostate apex to isodose lines was also found to be significant in predicting stricture formation. CONCLUSION: There was evidence to suggest that the development of BXT-related stricture was associated with radiation dose at the apical and peri-apical urethra. Attention to the dose delivered to those areas may minimise the risk of developing such morbidity.

Novel prostate brachytherapy technique: improved dosimetric and clinical outcome.

PURPOSE: Erectile dysfunction following prostate brachytherapy is reported to be related to dose received by the penile bulb. To minimise this, whilst preserving prostate dosimetry, we have developed a technique for I-125 seed brachytherapy using both stranded seeds and loose seeds delivered with a Mick applicator, and implanted via the sagittal plane on trans-rectal ultrasound. MATERIALS AND METHODS: Post-implant dosimetry and potency rates were compared in 120 potent patients. In Group 1, 60 patients were treated using a conventional technique of seeds implanted in a modified-uniform distribution. From January 2005, a novel technique was developed using stranded seeds peripherally and centrally distributed loose seeds implanted via a Mick applicator (Group 2). The latter technique allows greater flexibility when implanting the seeds at the apex. Each patient was prescribed a minimum peripheral dose of 145 Gy. No patients received external beam radiotherapy or hormone treatment. There was no significant difference in age or pre-implant potency score (mean IIEF-5 score 22.4 vs. 22.6, p=0.074) between the two groups. RESULTS: The new technique delivers lower penile bulb doses (D(25) as %mPD - Group 1: 61.2+/-35.7, Group 2: 29.7+/-16.0, p<0.0001; D(50) as %mPD - Group 1: 45.8+/-26.9, Group 2: 21.4+/-11.7, p<0.0001) whilst improving prostate dosimetry (D(90) - Group 1: 147 Gy+/-21.1, Group 2: 155 Gy+/-16.7, p=0.03). At 2 years, the potency rate was also improved: Group 1: 61.7%; Group 2: 83.3% (p=0.008). CONCLUSIONS: In this study, the novel brachytherapy technique using both peripheral stranded seeds and central loose seeds delivered via a Mick applicator results in a lower penile bulb dose whilst improving prostate dosimetry, and may achieve higher potency rates.