Clinical feasibility of combining intraoperative electron radiation therapy with minimally invasive surgery: a potential for electron-FLASH clinical development.

BACKGROUND: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. METHODS: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. RESULTS: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. CONCLUSIONS: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams.

Practice-oriented solutions integrating intraoperative electron irradiation and personalized proton therapy for recurrent or unresectable cancers: Proof of concept and potential for dual FLASH effect.

Background: Oligo-recurrent disease has a consolidated evidence of long-term surviving patients due to the use of intense local cancer therapy. The latter combines real-time surgical exploration/resection with high-energy electron beam single dose of irradiation. This results in a very precise radiation dose deposit, which is an essential element of contemporary multidisciplinary individualized oncology. Methods: Patient candidates to proton therapy were evaluated in Multidisciplinary Tumor Board to consider improved treatment options based on the institutional resources and expertise. Proton therapy was delivered by a synchrotron-based pencil beam scanning technology with energy levels from 70.2 to 228.7 MeV, whereas intraoperative electrons were generated in a miniaturized linear accelerator with dose rates ranging from 22 to 36 Gy/min (at Dmax) and energies from 6 to 12 MeV. Results: In a period of 24 months, 327 patients were treated with proton therapy: 218 were adults, 97 had recurrent cancer, and 54 required re-irradiation. The specific radiation modalities selected in five cases included an integral strategy to optimize the local disease management by the combination of surgery, intraoperative electron boost, and external pencil beam proton therapy as components of the radiotherapy management. Recurrent cancer was present in four cases (cervix, sarcoma, melanoma, and rectum), and one patient had a primary unresectable locally advanced pancreatic adenocarcinoma. In re-irradiated patients (cervix and rectum), a tentative radical total dose was achieved by integrating beams of electrons (ranging from 10- to 20-Gy single dose) and protons (30 to 54-Gy Relative Biological Effectiveness (RBE), in 10-25 fractions). Conclusions: Individual case solution strategies combining intraoperative electron radiation therapy and proton therapy for patients with oligo-recurrent or unresectable localized cancer are feasible. The potential of this combination can be clinically explored with electron and proton FLASH beams.

Corrigendum: Practice-oriented solutions integrating intraoperative electron irradiation and personalized proton therapy for recurrent or unresectable cancers: Proof of concept and potential for dual FLASH effect.

[This corrects the article DOI: 10.3389/fonc.2022.1037262.].

Oncological safety of transanal total mesorectal excision (TaTME) for rectal cancer: mid-term results of a prospective multicentre study.

BACKGROUND: There is no consensus regarding the gold standard technique for rectal cancer as Total Mesorectal Excision (TME) may be safely performed either by open or minimally invasive surgery. The laparoscopic approach, however, may carry technical difficulties. For this reason, a novel technique has emerged in the last decade combining a dual laparoscopic dissection (abdominal and transanal) to perform the TME technique (TaTME). When focusing on oncological outcomes, there is a lack of literature regarding mid-long term results. The aim of this study is to evaluate the mid-term oncological impact of TaTME for treating rectal cancer. METHODS: A prospective multicentre study was performed in four tertiary centres including consecutive patients who underwent TaTME for mid-low rectal cancer by the same group of experienced surgeons. The analysed data included pathological results on the quality of TME and mid-term oncological outcomes. RESULTS: In total, 173 patients were included throughout a study period of 6 years. Our series included 70% males and 68% of patients with neoadjuvant treatments. The median follow-up was 23 [15-37.5] months. Regarding pathological results, a complete TME was achieved in 72.8%, while circumferential and distal margins were affected in 1.4 and 1.1%, respectively. Five patients developed local recurrences (3%) and 8.1% presented distant disease during the follow-up. The 2-year disease-free survival and the overall survival rates were 88% and 95%, respectively. CONCLUSIONS: There is currently a lack of evidence in the literature regarding TaTME and oncological outcomes with no data available from randomized clinical trials. In the meantime, the reported results from different multicentre series are controversial. This study showed positive mid-term outcomes at 2 years of follow-up and supported notable oncological outcomes with TaTME. However, it must be emphasized that previous experience in minimally invasive and transanal surgeries is essential for surgeons before intending to perform TaTME.

Liver prometastatic reaction: Stimulating factors and responsive cancer phenotypes.

Cancer is first a localized tissue disorder, whose soluble and exosomal molecules and invasive cells induce a host response providing the stromal components of the primary tumor microenvironment (TME). Once the TME is developed, cancer-derived molecules and cells can more efficiently spread out and a whole-body response takes place, whose pathophysiological changes may result in a paraneoplastic syndrome. Remote organ-specific prometastatic reactions may also occur at this time, facilitating metastatic activities of circulating tumor cells (CTCs) through premetastatic niche development at targeted organs. However, additional signaling factors from the inter-organ communication network involved in the pathophysiology and comorbidities of cancer patients may also regulate prometastatic reaction-stimulating effects of cancer and non-cancer tissue factors. This article provides a conceptual overview of our ongoing clinical research on the liver prometastatic reaction (LPR) of patients with colorectal cancer (CRC), their portal vein- and hepatic artery-driven LPR-Stimulating Factors (LPR-SF), and their resulting LPR-derived Metastasis-Stimulating Factors (LPR-MSF) acting on liver-invading CRC cells. In addition, we also provide new insights on the molecular subtyping of LPR-responsive cancer phenotypes in patients with CRC and melanoma; and on how to investigate and interpret the prometastatic infrastructure in the real pathophysiological context of patients with cancer undergoing surgical procedures and receiving pharmacological treatments with multiple side effects, including those affecting the LPR, its stimulating factors and responsive cancer phenotypes.

What Should We Expect After a Complete Cytoreduction at the Time of Interval or Primary Debulking Surgery in Advanced Ovarian Cancer?

PURPOSE: To compare the impact, in terms of survival, of complete cytoreduction after primary debulking surgery (PDS) and interval debulking surgery (IDS) in patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stages III-IV) by reviewing the recent literature. METHODS: A search of the PubMed database during the last 7 years (2008-2014) was carried out looking for studies specifically showing data on median survival or disease-free survival after complete cytoreduction after either PDS or IDS. RESULTS: We found 24 publications including 14,182 patients with stages III to IV ovarian cancer. A total of 11871 patients (83.7 %) underwent PDS and 2311 (16.3 %) underwent interval debulking after neoadjuvant chemotherapy. A total of 4684 patients (33 %) were considered completely resected with microscopic residual disease. After PDS, the weighted average of median overall and progression-free survival was 43 and 17 months, respectively, for the whole group. After IDS, median and progression-free survival were 33 and 14 months. The rate of complete cytoreduction after PDS was inferior to the obtained in patients with IDS (27 vs. 59 %). However, the median survival in patients with complete cytoreduction with primary cytoreduction was 23 months longer than in the group with interval debulking (69 vs. 45 months). CONCLUSIONS: Complete cytoreduction after IDS yields a inferior outcome in terms of median survival than PDS of almost 2 years. Despite the higher rate of complete resection, IDS apparently fails to improve the results obtained by primary debulking.

Hysteroscopic surgery for conservative management in endometrial cancer: a review of the literature.

Endometrial cancer is the most common gynaecologic malignancy, usually diagnosed in postmenopausal women. However, an incidence rate of 2-14% of cases consisting of women under the age of 45 years old has been reported. Multiple reports have described the conservative treatment of this tumour in selected patients with the objective of preserving fertility. In this article, we review the literature to evaluate the results of conservative treatment of endometrial cancer with hysteroscopic resection.

Ileal orthotopic neobladder after pelvic exenteration for cervical cancer.

OBJECTIVE: We aimed to describe our preliminary experience in creating an ileal orthotopic urinary conduit in patients with a history of pelvic irradiation undergoing pelvic exenteration for recurrent cervical cancer and to evaluate the feasibility, complication rates, and outcomes of this procedure. METHODS: A retrospective chart review was performed in all 6 patients who underwent ileal orthotopic neobladder creation at our institution between January 2005 and March 2008. Main outcome measures were surgical complications, continence rate, neobladder function, and oncologic outcome. RESULTS: The mean patient age was 46.6 years (range, 38-61). Four patients underwent anterior exenteration and 2 total pelvic exenterations. There were no intraoperative complications. The median operative time was 456 min (range, 372-600). The median time to create the orthotopic urinary conduit was 70 min (range, 55-90). Three patients had postoperative neobladder anastomotic leak. Two of them had this complication successfully managed conservatively and 1 surgically. Daytime urinary continence was good or satisfactory in 4 of 6 patients. Nighttime urinary continence was good or satisfactory in 3 of 6 patients. All patients reported being satisfied with their decision to undergo this procedure. Median follow-up time was 20.5 months (range, 6-34). At last visit, 3 patients were alive without evidence of disease, 1 was alive with stable retroperitoneal disease, and 2 had died of disease recurrence after exenteration. CONCLUSIONS: Ileal orthotopic neobladder creation in patients undergoing exenteration for recurrent cervical cancer is feasible after radiation. The rate of urinary continence is acceptable.

Sparing fertility in young patients with endometrial cancer.

The objective of this review is to recognize the characteristics of endometrial adenocarcinoma in young patients and to evaluate the published experience with conservative approach in patients with endometrial adenocarcinoma. We searched MEDLINE articles describing patients with endometrial adenocarcinoma who were treated with hormonal therapy. The search included articles published between January 1966 and January 2007. Endometrial carcinoma in patients under 45 years of age is an unusual condition that shows a more favorable pattern than in older patients. One hundred thirty three patients were found in the search. The average duration of hormonal therapy was approximately 6 months. The average response time was 12 weeks. Seventy six percent of patients treated with hormonal therapy had a complete response and the other 24% never responded to treatment. Of those who initially responded, 66% didn't show recurrence of disease. The other 34% had a relapse. There have been published 4 deaths of patients conservatively managed. A conservative approach in these patients can offer reasonable oncological security and the opportunity of fulfilling their maternal desires in selected cases. However, consideration should be taken regarding the potential adverse outcomes that have been recently published in the literature.

Surgical treatment of recurrent cervical cancer: state of the art and new achievements.

This article review the current situation of the exenterative procedures as part of the treatment of recurrent cervical cancer after radiation. Pelvic exenteration has been proven the only curative choice of treatment in selected cases of this clinical situation. A review of historical and recent published series have shown an increase of 5-y survival from 30 to 42 %. Almost one out of two patients will suffer complications of some kind, and one out of three will have a severe complication with pelvic exenteration. During the past sixty years, a number of outstanding improvements have been achieved - not only in surgical outcomes, but also in quality of life - owing to new reconstructive approaches. Women facing an exenterative procedure must be counseled carefully about the risks and long-term concerns related to the procedure. Each should undergo a comprehensive evaluation to make sure there is no evidence of unresectable or metastatic disease that would make her an unsuitable candidate for exenteration.

The current role of neoadjuvant chemotherapy in the management of cervical carcinoma.

The role of neoadjuvant chemotherapy (NACT) in cervical cancer has been a matter of investigation over the last 20 years. A systematic review and meta-analysis of individual patient data (IPD) demonstrated that NACT followed by surgery is superior to radiotherapy alone in terms of overall survival. However, in spite of the results of the meta-analysis, NACT has not been adopted as the new standard of care. In the present paper, we review the reasons why NACT is still considered an investigational approach in cervical cancer.

Massive thyroid tumoral embolism from a breast carcinoma presenting as acute thyroiditis.

We describe an unusual case of metastatic disease to the thyroid, characterized by massive intra-arterial embolization and clinical presentation as acute thyroiditis. The patient, a 37-year-old woman with a history of breast carcinoma, presented clinically with acute thyroiditis. No nodules were palpable, and fine-needle aspiration cytology of the left lobe was performed. It showed a pleomorphic carcinoma and was followed by total thyroidectomy. Histology disclosed a pleomorphic carcinoma diffusely affecting the thyroid gland. It was characterized by an extensive intra-arterial tumoral embolization. Immunohistochemistry confirmed the metastatic nature of the neoplasm. This is a very uncommon form of metastatic disease to the thyroid. The ischemia and necrosis associated with the embolic process were most probably responsible for this clinical presentation. This atypical clinical and cytologic presentation may induce confusion with a primary neoplasm, mainly anaplastic thyroid carcinoma.