Optical diagnostic imaging and therapy for thyroid cancer.

Thyroid cancer, as one of the most common endocrine cancers, has seen a surge in incidence in recent years. This is most likely due to the lack of specificity and accuracy of its traditional diagnostic modalities, leading to the overdiagnosis of thyroid nodules. Although there are several treatment options available, they are limited to surgery and 131I radiation therapy that come with significant side effects and hence cannot meet the treatment needs of anaplastic thyroid carcinoma with very high malignancy. Optical imaging that utilizes optical absorption, refraction and scattering properties, not only observes the structure and function of cells, tissues, organs, or even the whole organism to assist in diagnosis, but can also be used to perform optical therapy to achieve targeted non-invasive and precise treatment of thyroid cancer. These applications of screening, diagnosis, and treatment, lend to optical imaging's promising potential within the realm of thyroid cancer surgical navigation. Over the past decade, research on optical imaging in the diagnosis and treatment of thyroid cancer has been growing year by year, but no comprehensive review on this topic has been published. Here, we review key advances in the application of optical imaging in the diagnosis and treatment of thyroid cancer and discuss the challenges and potential for clinical translation of this technology.

Merkel cell carcinoma: Epidemiology, disease presentation, and current clinical practice outcomes.

Using the National Cancer Database, we introduce the findings of a retrospective investigation of the largest cohort of cases with Merkel cell carcinoma (N = 20,829). A decreasing proportion of stage I (P = .0004) and stage II (P = .0065) Merkel cell carcinoma among skin cancers was complemented by an increasing proportion of stage III disease (P < .0001). A predominance of non-Hispanic White (96.4%), male (62.6%) patients with a mean age of 74.5 ± 10.8 years and Medicare coverage (73.5%) was observed. Stage I was the most common presenting stage at diagnosis (29.2%), followed by stages II (12.7%), III (11.0%), and IV (3.8%). Most Merkel cell carcinoma tumors grew outside the head and neck (53.4%) and showed a nodular growth pattern (66.0%) but no extracapsular lymph node (90.5%) or lymphovascular involvement (63.8%). Narrow-margin excision and radiation therapy (RT) were used in 75.2% and 56.3% of tumors, respectively. Wide-margin excision lead to improved overall survival (P < .001) versus narrow-margin excision, particularly in stage III (difference in the median overall survival rate [ΔmOS], 23.7 months; P < .001). RT showed a significant OS benefit (P =.006), most pronounced in stage II (ΔmOS, 37.8 months) followed by stage I (ΔmOS, 16.1 months; P < .001). The survival benefit with primary-site RT (ΔmOS, 24.0 months) was higher than that with primary-site/lymph node RT (ΔmOS, 5.2 months; P < .001). Wide-margin excision independently predicted improved OS (hazard ratio, 0.577; 95% CI, 0.403-0.826; P = .003) versus narrow-margin excision and RT predicted better OS (hazard ratio, 0.608; 95% CI, 0.424-0.873; P = .007) versus no RT on multivariable analysis.

Single fraction of HDR brachytherapy for prostate cancer: Results of the SiFEPI phase II prospective trial.

Purpose: To report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial. Materials/Methods: The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated. Results: From 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46-79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64-86], 6y-bRFS, lRFS and mRFS were 62 % [45-85], 61 % [44-85] and 93 % [85-100] respectively while 6y-DFS, CSS and OS were 54 % [37-77], 100 % and 89 % [77-100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24-69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence. Conclusions: Long-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

High-dose-rate brachytherapy boost for elderly patients with intermediate to high-risk prostate cancer: 5-year clinical outcome of the PROSTAGE cohort.

Purpose: To analyze the oncological outcome in elderly (>70 years) prostate cancer after high-dose rate brachytherapy (HDB) boost. Materials/methods: In this retrospective study, patients with intermediate (IR) and high-risk (HR) prostate cancer underwent external beam radiation therapy (EBRT) followed by HDB boost with/without androgen deprivation therapy (ADT). The impact of age (≤70y vs. > 70y) was investigated. Oncological outcome focused on biochemical relapse-free survival (bRFS), cause-specific (CSS) and overall survival (OS). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were investigated. Results: From 07/08 to 01/22, 518 pts received a HDB boost, and 380 were analyzed (≤70y:177pts [46.6%] vs. > 70y:203pts [53.4%]). Regarding NCCN classification, 98 pts (≤70y: 53pts; >70y: 45pts; p = 0.107) and 282 pts (≤70y: 124pts; >70y: 158pts; p = NS) were IR and HR pts respectively. Median EBRT dose was 46 Gy [37.5-46] in 23 fractions [14-25]. HDB boost delivered a single fraction of 14/15 Gy (79%). ADT was used in 302 pts (≤70y: 130pts; >70y: 172pts; p = 0.01). With MFU of 72.6 months [67-83] for the whole cohort, 5-y bRFS, 5-y CSS and 5-y OS were 88% [85-92], 99% [97-100] and 94% [92-97] respectively; there was no statistical difference between the two age groups except for 5-y CSS (p = 0.05). Late GU and GI toxicity rates were 32.4% (G ≥ 3 7.3%) and 10.1% (no G3) respectively. Conclusions: For IR and HR prostate cancers, HDB boost leads to high rates of disease control with few late G ≥ 3 GU/GI toxicities. For elderly pts, HDB boost remains warranted mainly in HR pts, while competing comorbidity factors influence OS.

Irradiation of localized prostate cancer in the elderly: A systematic literature review.

Purpose: To analyze the literature that addresses radiation therapy for intermediate and high-risk prostate cancer (PC) in the elderly. Patients and methods: A PubMed literature search was conducted including articles from 01/01/2000 to 30/06/21, with the following keywords: PC, radiotherapy/brachytherapy and elderly. The analysis mainly focused on the issue of under-treatment in the elderly and the benefit/risk balance of irradiation. Results: Of the 176 references analyzed, 24 matched the selection criteria. The definition of "elderly patient" varied from 70 to 80 years. The analysis was impacted by the inhomogeneous primary end points used in each cohort. Age was often an obstacle to radical treatment, with a subsequent risk of under-treatment, particularly in patients with a poorer prognosis. However, comparable elderly oncological outcomes were compared to younger patients, both with external beam radiotherapy alone or combined with brachytherapy boost. Late toxicity rates are low and most often comparable to younger populations. However, a urinary over- toxicity was observed in the super-elderly (>80 years) after brachytherapy boost. The use of ADT should be considered in light of comorbidities, and may even be deleterious in some patients. Conclusion: Due to the increase in life expectancy, the management of PC in the elderly is a challenge for patients, clinicians and health insurance payers. Except for unfit men, elderly patients remain candidates for optimal curative treatment (i.e. regardless of age) after oncogeriatric assessment. More solid data from prospective trials conducted specially in this population will provide better guidance in our daily clinical practice.

Disparities in cancer-specific and overall survival in black women with endometrial cancer: A Medicare-SEER study.

OBJECTIVES: To examine overall survival (OS) and cancer-specific survival (CSS) for different racial groups of women with surgically staged endometrial cancer by histologic subtype. METHODS: This is a retrospective cohort study of women with stage I-III endometrioid, serous, clear cell, and carcinosarcoma who underwent hysterectomy as primary surgical staging in the 2000-2016 SEER-Medicare database. OS and CSS outcomes were stratified by race (defined as White, Black, Other), stage, and histology. Survival was assessed with descriptive analyses, log-rank tests and unadjusted and adjusted multivariable cox regression models. RESULTS: Of the 24,142 women identified, 85.5% were White, 8.5% Black, and 6% other races. Receipt of adjuvant therapy differed only for stage III endometrioid: Black women were less likely to receive adjuvant treatment after hysterectomy (61.2% vs. 70.1% White, p = 0.03). For stage I, Black women had worse CSS for all histologies other than clear cell in unadjusted and adjusted analyses. For stage II, Black women had worse CSS for endometrioid histology in unadjusted analyses and similar OS. For stage III, Black women with endometrioid carcinoma had worse CSS and OS in unadjusted analyses, but no significant difference in CSS in adjusted analyses. "Other" race showed improved OS for Stage I endometrioid adenocarcinoma without significant differences in outcomes when compared to White women. CONCLUSION: Across histologies other than clear cell, Black women diagnosed with stage I endometrial cancer had consistently worse CSS, despite similar receipt of adjuvant therapy. Differences in CSS and OS at higher stages disappeared once accounting for treatment disparities.

Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life.

AIMS: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). METHODS: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). DISCUSSION: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. TRIAL REGISTRATION: NCT number: NCT04891471.

High-dose rate brachytherapy in localized penile cancer: 5-Year clinical outcome analysis.

PURPOSE: To analyze the oncological outcome and toxicity profile after conservative treatment based on multicatheter interstitial high-dose rate brachytherapy (MHB) for patients presenting a localized penile cancer. MATERIALS AND METHODS: Patients with histologically proven, non-metastatic (T1-T2 N0-N2 M0) localized penile cancer were treated with MHB. Needles were placed under general anesthesia into the target volume using a dedicated template. Treatment planning was performed using a post-implant CT-scan to deliver 35 Gy or 39 Gy (9f, 5d) for adjuvant or definitive treatment respectively. Five-year oncological outcome was evaluated with local relapse-free (LRFS), regional relapse-free (RRFS), and metastasis-free survival (MFS), specific (SS) and overall survival (OS). In pre-treatment and follow-up consultations, skin, urinary and sexual toxicities were investigated using CTCAEv4.0 classification, International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5-items (IIEF-5). Dosimetry data were also analyzed. RESULTS: From 03/2006 to 05/2020, with a median follow-up of 72.4 months [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], 29 pts, mainly T1 (75.9%) and N0 (89.7%), underwent MHB. Eleven (38%) and 18 pts (62%) received MHB as adjuvant or definitive treatment respectively. Five-year LRFS, RRFS, MFS, SS and OS were 82%, 82%, 89%, 88% and 73% respectively. Six patients (20.7%) experienced local relapse and underwent salvage penectomy leading to a penile preservation rate of 79.3%. Acute skin toxicity was reported 1 month after MHB, with 28% G1, 66% G2 and 6% G3. Late skin complications were telangiectasia for 5 pts (17%) and necrosis for 3 pts (10.3% requiring hyperbaric oxygen therapy). Comparing pre- and post-treatment status, no significant change was observed for skin appearance, IPSS and IIEF-5. CONCLUSION: MHB represents an efficient first line conservative treatment option for early penile cancers. Oncological outcome and late toxicity profile appear encouraging. However, larger-scale cohorts with longer follow-up are needed to more accurately precise the features of the best candidate to MHB.

Limb-salvage surgery offers better five-year survival rate than amputation in patients with limb osteosarcoma treated with neoadjuvant chemotherapy. A systematic review and meta-analysis.

BACKGROUND: Osteosarcoma is the most common primary bone sarcoma. Currently, the main treatment option for high-grade osteosarcomas is neoadjuvant chemotherapy, followed by surgical resection of the lesion and adjuvant chemotherapy. Limb salvage surgery (LSS) and amputation are the main surgical techniques; however, controversy still exists concerning the best surgical method. Our meta-analysis compared the effectiveness of LSS and amputation combined with neoadjuvant chemotherapy in patients with limb osteosarcoma, in terms of 5-year overall survival (OS), 5-year disease-free survival (DFS) and local recurrence rate. METHODS: Following the established methodology of PRISMA guidelines, a literature search was conducted in PubMed, Cochrane, Google Scholar from 1975 until January 2020. Two independent reviewers evaluated the study quality based on the Newcastle-Ottawa scale. Odds ratio and 95% confidence interval of the OS, DFS and local recurrence rate were calculated. RESULTS: Thirteen studies were finally included with a total of 2884 patients; 1986 patients undergone LSS and 898 amputations. Five-year overall survival was almost 2-fold in patients treated with LSS than those treated with amputation (OR: 1.99; 95% CI: 1.35-2.93; I2 = 74%, p < 0.001). No difference was found in 5-year DFS between LSS patients and amputees (OR: 1.24; 95% CI: 0.55-2.79; I2 = 67%, p = 0.01). The odds of local recurrence was numerically higher in LSS compared to amputation but not statistically significant (OR: 2.29; 95% CI: 0.95-5.53; I2 = 47%, p = 0.05). However, the included studies did not clearly define differences in the stages of patients of the two groups. CONCLUSION: Our study demonstrated that in patients with limb osteosarcoma treated with neoadjuvant chemotherapy, LSS is associated with a higher 5-year overall survival and the odds of local recurrence may be increased but these results should be interpreted with caution due to high heterogeneity.

Transitioning from conformal radiotherapy to intensity-modulated radiotherapy after radical prostatectomy: Clinical benefit, oncologic outcomes and incidence of gastrointestinal and urinary toxicities.

AIM: The purpose of this study was to review genitourinary (GU) and gastrointestinal (GI) toxicity associated with high-dose radiotherapy (RT) delivered with 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) or volumetric arc therapy (VMAT) following radical prostatectomy (RP). BACKGROUND: RP is a therapeutic option for the management of prostate cancer (PrCa). When assessing postoperative RT techniques for PrCa, the published literature focuses on patients treated with 2-dimensional conventional methods without reflecting the implementation of 3D-CRT, IMRT, or VMAT. MATERIALS AND METHODS: A total of 83 patients were included in this analysis; 30 patients received 3D-CRT, and 53 patients received IMRT/VMAT. Acute and late symptoms of the GU and lower GI tract were retrospectively graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer radiation toxicity grading systems. The relapse failure-free rate and overall survival were also evaluated. RESULTS: The rate of acute GU toxicity was 9.4% vs. 13.3% for the IMRT/VMAT and 3D-CRT groups (p = 0.583). The 5-year actuarial rates of late GI toxicity for IMRT/VMAT and 3D-CRT treatments were 1.9% and 6.7%, respectively. The rate of late GU toxicity for the IMRT/VMAT and 3D-CRT treatment groups was 7.5% and 16.6%, respectively (p = 0.199). We found no association between acute or late toxicity and the RT technique in univariate and multivariate analyses. CONCLUSION: Postprostatectomy IMRT/VMAT and 3D-CRT achieved similar morbidity and cancer control outcomes. The clinical benefit of highly conformal techniques in this setting is unclear although formal analysis is needed.

Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management.

Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

Serum folate concentrations at diagnosis are associated with hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort study.

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.