Cardiac Dose Control and Optimization Strategy for Left Breast Cancer Radiotherapy With Non-Uniform VMAT Technology.

Purpose: A novel in-house technology "Non-Uniform VMAT (NU-VMAT)" was developed for automated cardiac dose reduction and treatment planning optimization in the left breast radiotherapy. Methods: The NU-VMAT model based on IGM (gantry MLC Movement coefficient index) was established to optimize the volumetric modulated arc therapy (VMAT) MLC movement and modulation intensity in certain gantry angles. The ESAPI embedded in Eclipse® was employed to connect TPS and the optimization program via I/O relevant DICOM RT files. The adjuvant whole-breast radiotherapy of 14 patients with left breast cancer was replanned using our NU-VMAT technology in comparison with VMAT and IMRT technology. Dosimetric parameters including D1%, D99%, and Dmean of PTV, V5, V10, and V20 of ipisilateral lung, V5, D20, D30, and Dmean of heart, monitor units (MUs), and delivery time derived from IMRT, VMAT, and NU-VMAT plans were evaluated for plan quality and delivery efficiency. The quality assurance (QA) was conducted using both point-dose and planar-dose measurements for all treatment plans. Results: The IGM-NU-VMAT curves with plan optimization (range from 50% to 147%) were converged more significantly than IGM-VMAT curves (range from 0% to 297%). The dose distribution requirements of the target and normal tissues could be met using IMRT, VMAT, or NU-VMAT; the lowest Dmean was achieved in NU-VMAT plans (5.38 ± 0.46 Gy vs 5.63 ± 0.61 Gy in IMRT and 7.95 ± 0.52 Gy in VMAT plans). Statistically significant differences were found in terms of delivery time and MU when comparing IMRT with VMAT and NU-VMAT plans (P < .05). In comparison with IMRT plans, the MU and delivery time in NU-VMAT plans dramatically decreased by 69.8% and 28.4%, respectively. Moreover, NU-VMAT plans showed a high gamma passing rate (96.5% ± 1.11) in plane dose verification and minimal dose difference (2.4% ± 0.19) in point absolute dose verification. Conclusion: Our non-uniform VMAT facilitated the treatment strategy optimization for left breast cancer radiotherapy with dosimetric advantage in cardiac dose reduction and delivery efficiency in comparison with the conventional VMAT and IMRT.

Radiotherapy management of rectal cancer in the backdrop of the COVID pandemic.

BACKGROUND: COVID-19 outbreak was declared as a pandemic by the World Health Organization in March 2020. Over the last 3 months, the pandemic has challenged the diagnosis and treatment of all cancer, including rectal cancer. Constraints in resources call for a change in the treatment strategy without compromising efficacy. RECENT FINDINGS: Delivery of shorter treatment schedules for radiotherapy offers advantages like short overall treatment time, improved throughput on the machine, improved compliance and reduced risk of transmission of COVID 19. Other strategies include delaying surgery, reducing the intensity of chemotherapy and adoption of organ preservation approach. CONCLUSION: The curative treatment of rectal cancer should not be hindered during the COVID pandemic, and modifications in the multi-modality treatment will help achieve quality care.

Mycotic keratitis due to Cylindrocarpon lichenicola: Successful salvage of the eye.

We hereby report a successfully salvaged eye due to mycotic keratitis by Cylindrocarpon lichenicola in a 60-year-old female from Kasaragod (Kerala). The patient came with a history of pain, photophobia and decreased vision of the right eye. The microbiological investigations of the corneal scraping revealed C. lichenicola. C. lichenicola is a soil saprophyte. Since the ulcer worsened paracentesis followed by therapeutic keratoplasty and adjunct therapy with natamycin drops, voriconazole drops and oral ketoconazole was given. We stress that evidence-based timely medical and surgical intervention helped in the restoration of the vision in an infected eye.

Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial.

PURPOSE: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. METHODS AND MATERIALS: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. RESULTS: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D98% (31.1 vs 30.8 Gy, P < .0001), PTV D2% (37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V50% (24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V90% (9.1% vs 10.4%, P = .0003) and V80% (13.2% vs 15.7%, P = .0003). CONCLUSIONS: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

Evidence-based nipple-sparing mastectomy in patients with higher body mass index: Recommendations for a successful standardized surgery.

Nipple-sparing mastectomy is used with increasing frequency in the multidisciplinary treatment of patients with operable breast cancer. This technique allows to remove the entire glandular tissue preserving the skin envelope and the nipple-areola complex. Common indications to nipple-sparing mastectomy include extensive or multicentric disease, inability to obtain clear surgical margins with breast conserving-surgery, large tumor size with respect to the breast size, as well as cases with contraindications for radiotherapy as well as patient preference. Higher body mass index may cause longer operative times and increased risk of complications such as nipple-areola complex and skin flap ischemia. Repetitive performance of standardized tasks could optimize oncological and aesthetic outcomes and increase the chance of success.

Effect of Surgical Specialty on Management of Adnexal Masses in Children and Adolescents: An 8-Year Single-Center Review.

STUDY OBJECTIVE: Children with adnexal masses might be managed by pediatric surgeons, urologists or gynecologists, with the potential for different management strategies between specialties. In this study we compared ovarian conservation rates and surgical approach for adnexal masses in children and adolescents managed either by pediatric surgeons/urologists or gynecologists at a tertiary care institution. DESIGN: Retrospective cohort review. SETTING: Tertiary pediatric and adult university hospital. PARTICIPANTS: Patients younger than 18 years of age with an adnexal mass managed surgically with removal of histologically confirmed ovarian or fallopian tube tissue from 2008 to 2015. INTERVENTIONS: Laparoscopic or open procedure for adnexal mass. MAIN OUTCOME MEASURES: The primary outcome was rate of ovarian conservation relative to surgical specialty. The secondary outcome was surgical approach relative to surgical specialty. RESULTS: Forty-eight patients underwent surgery for adnexal masses; 26 (54%) under pediatric surgery/urology and 22 (46%) under gynecology care. Laparoscopy was performed in 5 (19%) pediatric and 19 (86%) gynecology cases (P = .000006). Of 24 patients older than 12 years of age with a benign tumor, 10 (42%) underwent procedures resulting in loss of an ovary with or without fallopian tube; 8 of these (80%) were under pediatric care. Of the remaining 14 (58%) who underwent ovarian conserving surgery, 12 (80%) were under gynecology care (P = .0027). CONCLUSION: Patients with a benign tumor were significantly more likely to undergo ovary-preserving surgery under gynecology care than under pediatric surgery/urology care. A multidisciplinary team approach involving gynecology and pediatric surgical specialties would be valuable in assessing the merits of ablative or conservative surgery in each case.

Segmental Ureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-analysis of Comparative Studies.

Radical nephroureterectomy (RNU) represents the standard of care for high-risk upper tract urothelial carcinoma (UTUC). In selected patients with ureteral UTUC, a conservative approach such as segmental ureterectomy (SU) can be considered. However, this therapeutic option remains controversial. The aim of this study was to perform a systematic review and meta-analysis of studies assessing the outcomes of SU versus RNU in patients with UTUC. Three search engines (Scopus, Embase, and Web of Science) were queried up to May 2019. The Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA Statement) was used as a guideline for study selection. The clinical question was established as stated in the PICO (Population, Intervention, Comparator, Outcome) process. Patients in the SU group were more likely to have history of bladder cancer (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.12-3.51; P = .02), but less likely to present with preoperative hydronephrosis (OR, 0.52; 95% CI: 0.31-0.88; P = .02). A higher rate of ureteral tumor location was found in the SU group (OR, 7.54; 95% CI, 4.15-13.68; P < .00001). The SU group presented with a lower rate of higher (pT ≥ 2) stage (OR, 0.66; 95% CI, 0.53-0.82; P = .0002), and high-grade tumors (OR, 0.62; 95% CI, 0.50-0.78; P < .0001). The SU group was found to have shorter 5-year relapse-free survival (OR, 0.64; 95% CI, 0.43-0.95; P = .03), but higher postoperative estimated glomular filtration rate (weighted mean difference, 10.97 mL/min; 95% CI, 2.97-18.98; P = .007). Selected patients might benefit from SU as a therapeutic option for UTUC. In advanced high-risk disease, RNU still remains the standard of care.

Systematic Review and Pooled Analysis of the Impact of Renorrhaphy Techniques on Renal Functional Outcome After Partial Nephrectomy.

Despite the important relationship between renorrhaphy and functional outcomes of partial nephrectomy, the urological guidelines do not provide recommendations about the optimal renorrhaphy technique. We carried out the first pooled literature analysis of the impact of suture technique on ultimate renal function after partial nephrectomy. Three studies comparing interrupted versus running suture including data on glomerular filtration rate (GFR) were included, for a total of 124 versus 269 patients. No significant differences were found between pre- and postoperative GFR in either patients who received an interrupted suture (weighted mean difference, -4.88ml/min, 95% confidence interval [CI] -11.38; 1.63, p=0.14) or those who received a running suture (-3.42ml/min, 95% CI -9.96; 3.12, p=0.31). Three studies comparing single- versus double-layer renorrhaphy included data on GFR (321 vs 199 patients). A benefit in functional outcomes favored single-layer technique (-3.19ml/min, 95% CI -8.09; 1.70, p=0.2 vs -6.07ml/min, 95% CI -10.75; -1.39, p=0.01). In conclusion, our quantitative synthesis suggests a renal functional benefit of the single-layer closure during partial nephrectomy. PATIENT SUMMARY: The available studies on renal functional data included in the present review suggest that "less is more" for renorrhaphy after partial nephrectomy. The single-layer renorrhaphy technique showed advantages in renal functional outcomes compared with the double-layer technique.

Targeted Intervention to Improve the Quality of Head and Neck Radiation Therapy Treatment Planning in the Netherlands: Short and Long-Term Impact.

PURPOSE: To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed. METHODS AND MATERIALS: A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases. RESULTS: Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable. CONCLUSIONS: Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols.

Has adherence to treatment guidelines for mid/low rectal cancer affected the management of patients? A monocentric study of 604 consecutive patients.

INTRODUCTION: In 2006 under the supervision of the French health authorities (HAS), recommendations for clinical practice (RCP) in the management of rectal cancers were first published. The primary objective of this study was to assess the impact of these guidelines on multidisciplinary management in terms of therapeutic strategies based on disease staging and quality indicators for surgical excision. Secondarily, we assessed the impact of the RCPs on postoperative and oncological outcomes. METHODS: All consecutive patients having undergone curative surgical excision for middle and low (subperitoneal) rectal cancer from 1995 to 2017 in the university hospital of Caen were included in accordance with the relevant French guidelines. They were divided into two groups: before (Gr1) and after (Gr2) 2006. For each group, a chart review was conducted on demographic variables, preoperative rectal tumor features, disease severity variables and quality of surgery variables. Postoperative and oncological outcomes were likewise assessed and compared between the two groups. RESULTS: Six hundred and four patients were included (Gr1, n=266; Gr2, n=338). Compliance with French guidelines significantly improved (i) use of magnetic resonance imaging (P<0.0001) and CT-scan (P<0.0001)]; (ii) organization of multidisciplinary tumor boards (P<0.0001) leading to suitable neo-adjuvant treatment plan classification (P<0.0001). Consequently, compliance improved widespread total mesorectal excision (P<0.0001), sphincter-sparing surgery (P=0,0005), and completeness of curative resection in the specimen (P<0.0001). Although postoperative 90-day mortality was similar, overall postoperative morbidity significantly increased in Gr2 (P<0.0001). Overall (P=0.0005) and disease-free survival (P=0.0016) of patients in Gr2 were significantly prolonged and correlated with a significant reduction in local and distant recurrences. CONCLUSION: Compliance with the relevant French guidelines improved the quality of multidisciplinary management of patients undergoing curative surgery for subperitoneal rectal cancer. However, further progress is still needed to render accession to the recommendations more comprehensive.

Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Breast conservation versus mastectomy in patients with T3 breast cancers (> 5 cm): an analysis of 37,268 patients from the National Cancer Database.

PURPOSE: Breast conservation therapy (BCT) is standard for T1-T2 tumors, but early trials excluded breast cancers > 5 cm. This study was performed to assess patterns and outcomes of BCT for T3 tumors. METHODS: We reviewed the National Cancer Database (NCDB) for noninflammatory breast cancers > 5 cm, between 2004 and 2011 who underwent BCT or mastectomy (Mtx) with nodal evaluation. Patients with skin or chest wall involvement were excluded. Patients having clinical T3 tumors were analyzed to determine outcomes based upon presentation, with those having pathologic T3 tumors, subsequently assessed, irrespective of presentation. Overall survival (OS) was analyzed using multivariable Cox proportional hazards models, with adjusted survival curves estimated using inverse probability weighting. RESULTS: After exclusions, 37,268 patients remained. Median age and tumor size for BCT versus Mtx were 53 versus 54 years (p < 0.001) and 6.0 versus 6.7 cm (p < 0.001), respectively. Predictors of BCT included age, race, location, facility type, year of diagnosis, tumor size, grade, histology, nodes examined and positive, and administration of chemotherapy and radiotherapy. OS was similar between Mtx and BCT (p = 0.36). This held true when neoadjuvant chemotherapy patients were excluded (p = 0.39). BCT percentages declined over time (p < 0.001), while tumor sizes remained the same (p = 0.77). Median follow-up was 51.4 months. CONCLUSIONS: OS for patients with T3 breast cancers is similar whether patients received Mtx or BCT, confirming that tumor size should not be an absolute BCT exclusion. Declining use of BCT for tumors > 5 cm in younger patients may be accounted for by recent trends toward mastectomy.

Oral cancers: Current status.

Oral cancer is a global disease. Despite a well elucidated tumour progression model, these cancers present late. Attempts at early detection by way of adjunctive diagnostic technologies and screening have not lived up to expectations in spite initial promise. Surgery is the mainstay of treatment. Treatment intensification by way of adjuvant radiation/chemo radiation is warranted for those with high risk features. Recent studies have explored intensification in those with intermediate risk factors in an attempt to improve outcomes. There has been generation of recent robust evidence that has influenced the need and extent of neck dissection. Neoadjuvant chemotherapy (NACT) may have a potential role in organ preservation and borderline resectable oral cancers. Recurrent tumours should be offered surgery whenever feasible while the addition of biological agents to chemotherapy gives best results in the palliative settings.

NCCN Guidelines Insights: Bladder Cancer, Version 5.2018.

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

Prostate focal therapy: the rule or exception?

PURPOSE OF REVIEW: Prostate focal therapy has the potential to preserve urinary and sexual function while eliminating clinically significant cancer in a subset of men with low-volume, organ-confined prostate cancer. This systematic review aims to examine current evidence to determine the efficacy and safety of focal therapy for standard clinical application. RECENT FINDINGS: Focal therapy reduces the rate of cancer progression and conversion to radical therapy in men on active surveillance for prostate cancer. As a strategy, success in focal therapy is heavily dependent on the use of imaging and targeted biopsies. Despite advances in these areas, there remains a small but significant risk of under-detecting clinically significant cancer. Similarly, under-estimation of tumor volume may contribute to infield recurrences and close attention must be paid to the ablation margin. Although long-term oncological outcomes remain lacking, focal therapy has a low complication rate, minimal impact on urinary continence and a moderate impact on erectile function. SUMMARY: With the appropriate expertise in imaging, targeted biopsy and targeted ablation, focal therapy is a good option in men with low-intermediate risk cancer who are willing to maximize their urinary and sexual function. However, close posttreatment surveillance and the possibility of conversion to whole gland therapy must be accepted.

Quality assurance analysis of hippocampal avoidance in a melanoma whole brain radiotherapy randomized trial shows good compliance.

BACKGROUND: Melanoma brain metastases (MBM) often cause morbidity and mortality for stage IV melanoma patients. An ongoing randomised phase III trial (NCT01503827 - WBRT-Mel) evaluates the role of adjuvant whole brain radiotherapy (WBRT) following local treatment of MBM. Hippocampal avoidance during WBRT (HA-WBRT) has shown memory and neurocognitive function (NCF) preservation in the RTOG-0933 phase II study. This study assessed the quality assurance of HA-WBRT within the WBRT-Mel trial according to RTOG-0933 study criteria. METHODS: Hippocampal avoidance was allowed in approved centres with intensity-modulated radiotherapy capability. Patients treated by HA-WBRT were not randomized within the WBRT arm. The RTOG 0933 contouring Atlas was used to contour hippocampi. In the trial co-ordinating centre, patients were treated with volumetric modulated arc therapy using complementary arcs; similar techniques were used at other sites. Dosimetric data were extracted retrospectively and analysed in accordance with RTOG 0933 study constraints criteria. RESULTS: Among the 215 patients accrued to the WBRT-Mel study between April 2009 and September 2017, 107 were randomized to the WBRT arm, 22 were treated by HA-WBRT in 4 centers. Eighteen patients were treated in the same centre. The median age was 65 years. The commonest (91%) HA-WBRT schema was 30 Gy in 10 fractions. Prior to HA-WBRT, 10 patients had been treated by surgery alone, six by radiosurgery alone, four by surgery and radiosurgery and two exclusively by simultaneous integrated boost concurrent to HA-WBRT. Twenty patients were treated with intention to spare both hippocampi and two patients had MBM close to one hippocampus and were treated with intention to spare the contralateral hippocampus. According to RTOG-0933 study criteria, 18 patients (82%) were treated within constraints and four patients (18%) had unacceptable deviation in just one hippocampus. CONCLUSIONS: This dosimetric quality assurance study shows good compliance (82%) according to RTOG-0933 study dosimetric constraints. Indeed, all patients respected RTOG hippocampal avoidance constraints on at least one hippocampus. In the futureanalysis of the WBRT-Mel trial, the NCF of patients on the observation arm, WBRT arm and with HA-WBRT arm will be compared.

Evaluation of a Completion Total Mesorectal Excision in Patients After Local Excision of Rectal Cancer: A Word of Caution.

Background: According to Dutch guidelines, locally excised, low-risk, pT1 or ypT0-1 rectal cancer should not necessarily be followed by completion total mesorectal excision (cTME) in contrast to rectal cancers with higher T stages or unfavorable features. This study evaluated cTME after local excision at a national level with possible determinants for decision-making. Methods: All patients in the Dutch Colorectal Audit (DCRA) who underwent local excision of rectal cancer between 2012 and 2015 were included. Guideline adherence for performing cTME was determined with univariate and multivariate analyses to identify factors related to noncompliance. Results: According to the guidelines, of 530 included patients, cTME was indicated in 283 (53%), and among those, was performed in 82 (29%). Guideline adherence for performing cTME improved significantly (P<.001), from 10% in 2012 to 44% in 2015. Lower Charlson comorbidity index in patients with high-risk pT1 rectal cancer and younger patients (aged 61-70 years vs ≥80 years) with pT≥2 rectal cancer were associated with increased performance of cTME (odds ratio [OR], 13.50; 95% CI, 1.39-131.32, and OR, 6.25; 95% CI, 1.83-21.31, respectively). Conclusions: In this population-based study from the Netherlands, only a minority of patients underwent cTME after local excision of rectal cancer with pathologic features indicating the need for further treatment according to the guidelines. Although the percentage of patients undergoing cTME increased over time, the study indicated a tendency toward rectal-preserving treatment with potential oncologic risks.