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Open Access
Identification of consensus head and neck cancer-associated microbiota signatures: a systematic review and meta-analysis of 16S rRNA and The Cancer Microbiome Atlas datasets
(Microbiology Society, 2024) Yeo, K.; Li, R.; Wu, F.; Bouras, G.; Mai, L.T.H.; Smith, E.; Wormald, P.-J.; Valentine, R.; Psaltis, A.J.; Vreugde, S.; Fenix, K.
Introduction. Multiple reports have attempted to describe the tumour microbiota in head and neck cancer (HNSC).Gap statement. However, these have failed to produce a consistent microbiota signature, which may undermine understanding the importance of bacterial-mediated effects in HNSC.Aim. The aim of this study is to consolidate these datasets and identify a consensus microbiota signature in HNSC.Methodology. We analysed 12 published HNSC 16S rRNA microbial datasets collected from cancer, cancer-adjacent and non-cancer tissues to generate a consensus microbiota signature. These signatures were then validated using The Cancer Microbiome Atlas (TCMA) database and correlated with the tumour microenvironment phenotypes and patient's clinical outcome.Results. We identified a consensus microbial signature at the genus level to differentiate between HNSC sample types, with cancer and cancer-adjacent tissues sharing more similarity than non-cancer tissues. Univariate analysis on 16S rRNA datasets identified significant differences in the abundance of 34 bacterial genera among the tissue types. Paired cancer and cancer-adjacent tissue analyses in 16S rRNA and TCMA datasets identified increased abundance in Fusobacterium in cancer tissues and decreased abundance of Atopobium, Rothia and Actinomyces in cancer-adjacent tissues. Furthermore, these bacteria were associated with different tumour microenvironment phenotypes. Notably, high Fusobacterium signature was associated with high neutrophil (r=0.37, P<0.0001), angiogenesis (r=0.38, P<0.0001) and granulocyte signatures (r=0.38, P<0.0001) and better overall patient survival [continuous: HR 0.8482, 95 % confidence interval (CI) 0.7758-0.9273, P=0.0003].Conclusion. Our meta-analysis demonstrates a consensus microbiota signature for HNSC, highlighting its potential importance in this disease.
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International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients
(SPRINGER, 2020) Teras, J.; Kroon, H.M.; Miura, J.T.; Kenyon-Smith, T.; Beasley, G.M.; Mullen, D.; Farrow, N.E.; Mosca, P.J.; Lowe, M.C.; Farley, C.R.; Potdar, A.; Daou, H.; Sun, J.; Carr, M.; Farma, J.M.; Henderson, M.A.; Speakman, D.; Serpell, J.; Delman, K.A.; Smithers, B.M.; et al.
BACKGROUND:Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS:ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS:Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS:ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.
Open Access
Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients
(Oxford University Press (OUP), 2023) Greijdanus, N.G.; Wienholts, K.; Ubels, S.; Talboom, K.; Hannink, G.; Wolthuis, A.; de Lacy, F.B.; Lefevre, J.H.; Solomon, M.; Frasson, M.; Rotholtz, N.; Denost, Q.; Perez, R.O.; Konishi, T.; Panis, Y.; Rutegård, M.; Hompes, R.; Rosman, C.; van Workum, F.; Tanis, P.J.; et al.
Background: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/ secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1). Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of −1.1 (95 per cent c.i. −9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (−28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.
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Malignant features present in pre-treatment lateral pelvic lymph nodes in low rectal cancer predict distant metastases and survival, but not local recurrences
(Elsevier BV, 2021) Kroon, H.; Dudi-Venkata, N.; Bedrikovetski, S.; Liu, J.; Haanappel, A.; Ogura, A.; Van de Velde, C.; Rutten, H.; Beets, G.; Thomas, M.; Kusters, M.; Sammour, T.
Background: Pre-treatment enlarged lateral lymph nodes (LLNs) in patients with low rectal cancer predict local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known what the impact on oncological outcomes is when malignant features are present in LLNs. Materials and Methods: An international multi-center cohort study at five tertiary referral centers in the Netherlands and Australia was conducted. All patients were diagnosed with low rectal cancer with or without LLNs on pre-treatment MRI and underwent n(C)RT followed by TME. LLNs were considered enlarged in case of a short-axis of ≥5mm on pre-treatment MRI. Malignant features in LLNs were defined as nodes with internal heterogeneity or border irregularity. Survival was estimated using the Kaplan-Meier method with the Mantel-Haenszel test. Three-year recurrences were evaluated with the Chi-square/Fisher's exact test. Results: A total of 213 patients were included. The majority was male (67.7%) with a median age of 64 years (range 20-89). Median pre-treatment LLN short-axis was 7mm (range 5-28), 52.2% of the LLNS had malignant features. After a median follow-up of 47 months, patients with enlarged LLNs (7-9mm and 10mm+) had a worse local recurrence-free survival (LRFS; p<0.0001), but similar distant metastatic-free (DMFS; p=0.30) and overall survival (OS; p=0.27) compared to patients with smaller LLNs (0-4 and 5-6mm). On the other hand, patients with malignant features in LLNs had a similar LRFS (p=0.20), but worse DMFS (p=0.004) and OS (p=0.006) compared to patients without malignant features in the LLNs. Similar patterns were seen upon three-year recurrence analysis (table). Conclusions: Malignant features present in LLNs on pre-treatment MRI are predictive for worse DMFS and OS, but not for local recurrences.
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Safety and efficacy of outpatient management for elderly patients with uncomplicated acute diverticulitis
(Elsevier, 2020) Kroon, H.M.; Juszczyk, K.; Ireland, K.; Hollington, P.; Thomas, B.
Open Access
Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study
(Elsevier BV, 2021) Glasbey, J.; Ademuyiwa, A.; Adisa, A.; AlAmeer, E.; Arnaud, A.P.; Ayasra, F.; Azevedo, J.; Minaya-Bravo, A.; Costas-Chavarri, A.; Edwards, J.; Elhadi, M.; Fiore, M.; Fotopoulou, C.; Gallo, G.; Ghosh, D.; Griffiths, E.A.; Harrison, E.; Hutchinson, P.; Lawani, I.; Lawday, S.; et al.
Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restrictions. Methods: This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Findings: Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.
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Minimally invasive surgery in elderly patients with rectal cancer: An analysis of the Bi-National Colorectal Cancer Audit (BCCA)
(Elsevier, 2020) van Harten, M.J.; Greenwood, E.B.; Bedrikovetski, S.; Dudi-Venkata, N.N.; Hunter, R.A.; Kroon, H.M.; Sammour, T.
Background: Advanced age is associated with worse outcomes after open rectal cancer surgery. However, not much is known about outcomes of minimally invasive surgery (MIS) in the elderly. The aim of this study was to evaluate safety and efficacy of MIS in elderly rectal cancer patients using the Bi-national Colorectal Cancer Audit (BCCA) data from Australia and New Zealand (ANZ). Methods: 3451 patients were included, divided into three groups: <50 years (n ¼ 364), 50e74 years (n ¼ 2157) and 75 years (n ¼ 930). Propensity-score matching was performed for the elderly group analysis to correct for differences in baseline characteristics. Results: MIS was performed in 52.9% of elderly patients, slightly lower than rates in <50 year and 50e74 year old groups (61% and 55.5%, respectively, p ¼ 0.022). Elderly patients had more postoperative complications (p < 0.0001) and had a longer length of hospital stay (LOS; median 11 vs. 8 days for both other groups; p < 0.0001). Elderly patients had higher (y)pT-stages compared to both other groups (p < 0.0001) and were less likely to receive adjuvant therapy (p < 0.0001). Propensity-score matched analysis of the elderly group showed a higher rate of superficial wound dehiscence and a longer LOS after open surgery compared to MIS (10.3% vs. 2.6%, p ¼ 0.030; 12 days vs. 9.5 days, p ¼ 0.001, respectively), with comparable short-term oncological outcomes. Conclusions: MIS is performed in just over half of elderly rectal cancer patients who are selected for elective rectal resection surgery in ANZ. When performed in the elderly, MIS appears safe and is associated with fewer wound complications and a shorter LOS.
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Outcomes of Minimally Invasive Versus Open Proctectomy for Rectal Cancer: A Propensity-Matched Analysis of Bi-National Colorectal Cancer Audit Data
(Lippincott, Williams & Wilkins, 2020) Bedrikovetski, S.; Dudi-Venkata, N.N.; Kroon, H.M.; Moore, J.W.; Hunter, R.A.; Sammour, T.
Background: Minimally invasive surgery is commonly used in the treatment of rectal cancer, despite the lack of evidence to support oncological equivalence or improved recovery compared with open surgery. Objective: This study aims to analyze prospectively collected data from a large Australasian colorectal cancer database. Design: This is a retrospective cohort study using propensity score matching. Setting: This study was conducted using data supplied by the Bi-National Colorectal Cancer Audit. Patients: A total of 3451 patients who underwent open (n = 1980), laparoscopic (n = 1269), robotic (n = 117), and transanal total mesorectal excision (n = 85) for rectal cancer were included in this study. Main outcome measure: The primary outcome was positive margin rates (circumferential resection margin and/or distal resection margin) in patients treated with curative intent. Results: Propensity score matching yielded 1132 patients in each of the open and minimally invasive surgery groups. Margin positivity rates and lymph node yields did not differ between groups. The open group had a significantly lower total complication rate (27.6% vs 35.8%, p < 0.0001), including a lower rate of postoperative small-bowel obstruction (1.2% vs 2.5%, p = 0.03). The minimally invasive surgery group had significantly lower wound infection rate (2.9% vs 5.0%, p = 0.02) and a shorter length of hospital stay (8 vs 9 days, p < 0.0001). There was no difference in 30-day mortality. Limitations: Results are limited by the quality of registry data entries. Conclusion: In this patient population, minimally invasive proctectomy demonstrated similar margin rates in comparison with open proctectomy, with a reduced length of stay but a higher overall complication rate. See Video Abstract at http://links.lww.com/DCR/B190.
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Four different ileorectal anastomotic configurations following total colectomy
(Wiley, 2020) Jolly, S.; Dudi-Venkata, N.N.; Hanna-Rivero, N.; Kroon, H.M.; Reid, F.S.W.; Sammour, T.
Ileorectal and ileosigmoid anastomoses are typically performed following total colectomy and subtotal colectomy, respectively. The current literature provides extensive description of more common anastomoses such as after right hemicolectomy or anterior resection. However, there is little focus in the literature on the ileorectal or ileosigmoid anastomotic technique, despite these anastomoses having a relatively high complication rate. The purpose of the current study is to describe four standardized ileorectal or ileosigmoid anastomotic configurations, with commentary on specific challenges and theoretical advantages and disadvantages of each.
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Pelvic Exenteration for Advanced Nonrectal Pelvic Malignancy PelvExCollaborative
(Wolters Kluwer Health, 2019) Kelly, M.E.; Ryan, E.J.; Aalbers, A.G.J.; Abdul, A.N.; Abraham-Nordling, M.; Alberda, W.; Antoniou, A.; Austin, K.K.; Baker, R.; Bali, M.; Baseckas, G.; Bednarski, B.K.; Beets, G.L.; Berg, P.L.; Beynon, J.; Biondo, S.; Bordeianou, L.; Bremers, A.B.; Brunner, M.; Buchwald, P.; et al.
Objective: To determine factors associated with outcomes following pelvic exenteration for advanced nonrectal pelvic malignancy. Background: The PelvEx Collaborative provides large volume data from specialist centers to ascertain factors associated with improved outcomes. Methods: Consecutive patients who underwent pelvic exenteration for nonrectal pelvic malignancy between 2006 and 2017 were identified from 22 tertiary centers. Patient demographics, neoadjuvant therapy, histopathological assessment, length of stay, 30-day major complication/mortality rate were recorded. The primary endpoints were factors associated with survival. The secondary endpoints included the difference in margin rates across the cohorts, impact of neoadjuvant treatment on survival, associated morbidity, and mortality. Results: One thousand two hundred ninety-three patients were identified. 40.4% (n ¼ 523) had gynecological malignancies (endometrial, ovarian, cervical, and vaginal), 35.7% (n ¼ 462) urological (bladder), 18.1% (n ¼ 234) anal, and 5.7% had sarcoma (n ¼ 74). The median age across the cohort was 63 years (range, 23–85). The median 30-day mortality rate was 1.7%, with the highest rates occurring following exenteration for recurrent sarcoma or locally advanced cervical cancer (3.3% each). The median length of hospital stay was 17.5 days. 34.5% of patients experienced a major complication, with highest rate occurring in those having salvage surgery for anal cancer. Multivariable analysis showed R0 resection was the main factor associated with long-term survival. The 3-year overall-survival rate for R0 resection was 48% for endometrial malignancy, 40.6% for ovarian, 49.4% for cervical, 43.8% for vaginal, 59% for bladder, 48.3% for anal, and 48.1% for sarcoma. Conclusion: Pelvic exenteration remains an important treatment in selected patients with advanced or recurrent nonrectal pelvic malignancy. The range in 3-year overall survival following R0 resection (40%–59%) reflects the diversity of tumor types.
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ASO Author Reflections: International Experience of Isolated Limb Infusion for Melanoma Shows Durable Response
(Springer Nature, 2019) Miura, J.T.; Kroon, H.M.; Zager, J.S.
Abstract unavailable
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Snapshot quiz 20/11
(Wiley, 2020) Kroon, H.M.; Wijnhoven, B.; Winter, D.
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Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic
(Elsevier BV, 2021) Collaborative, C.
Introduction: Surgical services are preparing to scale-up in areas affected by COVID-19. This study aimed to evaluate the association between preoperative SARS-CoV-2 testing and postoperative pulmonary complications in patients undergoing elective cancer surgery. Methods: International cohort study including adult patients undergoing elective surgery for cancer in areas affected by SARS-CoV-2 up to 19 April 2020 (NCT04384926). Patients suspected preoperatively of SARS-CoV-2 infection were excluded. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery. Preoperative testing strategies were adjusted for confounding using mixed-effects models. Results: Of 8784 patients (432 hospitals, 53 countries), 2303 patients (26.2%) underwent preoperative testing: 1458 (16.6%) had a swab test, 521 (5.9%) CT only, and 324 (3.7%) swab and CT. The overall pulmonary complication rate was 3.9% and SARS-CoV-2 infection rate was 2.6%. After risk adjustment, only a nasopharyngeal swab test (adjusted odds ratio 0.68, 95% confidence interval 0.68-0.98, p¼0.040) was associated with lower rates of pulmonary complications. Swab testing remained beneficial before major surgery and in high SARS-CoV-2 population risk areas but not before minor surgery in low incidence areas. For a swab test, the number needed to test to prevent one pulmonary complication increased across major and minor surgery in high incidence areas (18 and 48 respectively), and major and minor surgery in low incidence areas (73 and 387 respectively). Discussion: Preoperative nasopharyngeal swab testing was beneficial before major surgery and in high SARS-CoV-2 incidence areas. There was no proven benefit of swab testing before minor surgery in low incidence areas.
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Isolated limb infusion for melanoma
(Springer, 2020) Beasley, G.; Miura, J.; Zager, J.; tyler, D.; Thompson, J.; Hidde, K.; Kroon, H.M.; Thompson, J.; Gershenwald, J.; Atkins, M.; Kirkwood, J.; McArthur, G.; Sober, A.; Halpern, A.; Garbe, C.; Scoyler, R.
Isolated limb infusion (ILI) using melphalan and dactinomycin (actinomycin D) was developed as a simplified and minimally invasive alternative to the traditional, more invasive, and elaborative isolated limb perfusion (ILP) to treat unresectable metastatic melanoma confined to the limb. An increasing number of centers around the world have reported their results using the procedure. Reports from different centers have shown that the procedure is safe, with mild-to-moderate regional toxicity, and results in satisfactory response rates. When comparing ILI and ILP, it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease, which decreases the likelihood of a favorable response. Even in this era of effective systemic therapies for metastatic melanoma, ILI is still worthwhile and a relatively straightforward, single-treatment option to treat locally recurrent or in-transit metastatic melanoma involving a limb. Due to its minimally invasive nature, ILI is an ideal platform to test new drugs and drug combinations. Potential exists to further improve ILI response rates when combined with novel therapies.
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Association Between Intraoperative Blood Glucose and Anastomotic Leakage in Colorectal Surgery
(Springer Science and Business Media LLC, 2021) Reudink, M.; Huisman, D.E.; van Rooijen, S.J.; Lieverse, A.G.; Kroon, H.M.; Roumen, R.M.H.; Daams, F.; Slooter, G.D.
Background Perioperative hyperglycemia is a known risk factor for postoperative complications after colorectal surgery. The aim of this study was to investigate whether intraoperative blood glucose values are associated with colorectal anastomotic leakage in diabetic and non-diabetic patients undergoing colorectal surgery. Methods This is an additional analysis of a previously published prospective, observational cohort study (the LekCheck study). Fourteen hospitals in Europe and Australia collected perioperative data. Consecutive adult patients undergoing colorectal surgery with primary anastomosis between 2016 and 2018 were included. From all patients, preoperative diabetic status was known and intraoperative blood glucose was determined just prior to the creation of the anastomosis. The primary outcome was the occurrence of anastomotic leakage within 30 days postoperatively. Results Of 1474 patients (mean age 68 years), 224 patients (15%) had diabetes mellitus, 737 patients (50%) had intraoperative hyperglycemia (≥126 mg/dL, ≥7.0 mmol/L), and 129 patients (8.8%) developed anastomotic leakage. Patients with intraoperative hyperglycemia had higher anastomotic leakage rates compared to patients with a normal blood glucose level (12% versus 5%, P<0.001). Anastomotic leakage rate did not significantly differ between diabetic and non-diabetic patients (12% versus 8%, P=0.058). Logistic regression analyses showed that higher blood glucose levels were associated with an increasing leakage risk in non-diabetic patients only. Conclusion Incidence and severity of intraoperative hyperglycemia are associated with anastomotic leakage in non-diabetic patients. Whether hyperglycemia is an epiphenomenon, a marker for other risk factors or a potential modifiable risk factor per se for anastomotic leakage requires future research.
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Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: the PelvEx II study
(Elsevier, 2021) Voogt, E.; Burger, P.
Background: A resection with clear resection margins (R0 resection) is the single most important prognostic factor for overall and local recurrence free survival in patients with locally recurrent rectal cancer (LRRC). However, despite the use of neoadjuvant chemo(re)irradiation, an R0 resection is achieved in only ±60% of patients. Induction chemotherapy in addition to neoadjuvant chemoradiotherapy is increasingly being used, as this combination may increase the R0 resection rate. Still, evidence for any beneficial effect of induction chemotherapy is lacking. Materials and Methods: We have set up an international, multicentre, open-label, phase III, parallel arms study that randomises patients in a 1:1 ratio to receive either induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Eligible patients are adults diagnosed with resectable LRRC after previous partial or total mesorectal resection, with a good performance status, without synchronous distant metastases, without recent chemo- and/or radiotherapy, or any contraindications for the planned study interventions. Induction chemotherapy consists of three 3-weekly cycles capecitabine with oxaliplatin (CAPOX) or four two-weekly cycles of 5-fluorouracil with leucovorin and oxaliplatin (FOLFOX) or 5-fluorouracil with leucovorin and irinotecan (FOLFIRI) (physician’s discretion). In case of stable or responsive disease, treatment is continued with one cycle CAPOX or two cycles FOLFOX/FOLFIRI. Radiotherapy dose is 25x2.0Gy or 28x1.8Gy in radiotherapy-naïve patients and 15x2.0Gy in previously irradiated patients. Concomitant chemotherapy agent is capecitabine 825mg/m2 twice daily on radiotherapy days. We hypothesized a 15% increase in the R0 resection rate in the experimental arm. With a 5% two-sided significance level, a power of 80% and a drop-out of 5%, a total of 364 patients is required. Results: The primary outcome is the rate of resections with clear margins (R0 resection). Secondary outcomes are local recurrence free survival, metastasis free survival, progression free survival, disease free, overall survival, radiological and pathological response, toxicity and compliance of neoadjuvant treatment, surgical morbidity, health-related costs and quality of life. Conclusions: This is the first randomised study that compares induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery with neoadjuvant chemoradiotherapy and surgery in patients with locally recurrent rectal cancer with the aim to improve surgical and oncological outcomes. The first inclusion is anticipated October 2020.
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Lateral lymph node dissection after neoadjuvant (chemo)radiotherapy may improve oncological outcomes in Western patients with low rectal cancer.
(American Society of Clinical Oncology (ASCO), 2020) Kroon, H.M.; Malakorn, S.; Dudi-Venkata, N.N.; Bedrikovetski, S.; Liu, J.; Bednarski, B.K.; Ogura, A.; Van De Velde, C.J.H.; Rutten, H.; Beets, G.; Thomas, M.; Kusters, M.; Chang, G.J.; Sammour, T.
In the West, rectal cancer patients with pre-treatment abnormal lateral lymph nodes (LLN) are commonly treated with neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Few centers perform lateral lymph node dissection (LLND) in addition to this, with the aim of improving oncological outcomes. To date, no comparative data are available in Western patients. Methods: An international multi-center cohort study was conducted comparing six centers from the Netherlands and Australia treating patients with abnormal LLN (≥5mm short-axis) with n(C)RT and TME (LLND- group) versus similarly staged patients from a dedicated cancer center in the USA who underwent a LLND in addition to n(C)RT and TME (LLND+ group). Results: Data were available on 169 patients. LLND+ patients (n = 44) consisted of significantly younger and more female patients with higher ASA-scores and ypN-stages compared to LLND- patients (n = 115). LLND+ patients also had a larger median LLN short-axis and were more likely to receive adjuvant chemotherapy (100 vs. 30%; p < 0.0001). Between groups, the lateral local recurrence rate (LLRR) was 0% for LLND+ vs. 7% for LLND- (p = 0.09) and the local recurrence rate (LRR) was 3% for LLND+ vs. 11% for LLND- (p = 0.13). No significant differences were observed in disease-free survival (DFS, p = 0.94) or overall survival (OS, p = 0.42). Sub-analysis of patients who underwent adjuvant chemotherapy (LLND- patients: n = 35) demonstrated clinically relevant though non-statistically significant trends towards a lower LLRR (0% for LLND+ vs. 6% for LLND-; p = 0.07), LRR (3% for LLND+ vs. 14% for LLND-; p = 0.06), DFS (p = 0.19) and OS (p = 0.17) in favour of the LLND+ group. Conclusions: Lateral lymph node dissection in addition to neoadjuvant (chemo)radiotherapy may improve oncological outcomes in Western patients with low rectal cancer and abnormal lateral lymph nodes.
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ASO Author Reflection: Isolated Limb Infusion for Locally Advanced Melanoma in the Extremely Old Patient is Safe and Effective
(Springer, 2020) Teras, J.; Kroon, H.M.; Zager, J.S.
Abstract unavailable
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Artificial intelligence for the diagnosis of lymph node metastases in patients with abdominopelvic malignancy: a systematic review and meta-analysis
(Elsevier BV, 2021) Bedrikovetski, S.; Dudi-Venkata, N.; Maicas, G.; Kroon, H.; Seow, W.; Carneiro, G.; Moore, J.; Sammour, T.
Background: Accurate clinical diagnosis of lymph node metastases is of paramount importance in the treatment of patients with abdominopelvic malignancy. This review assesses the diagnostic performance of deep learning algorithms and radiomics models for lymph node metastases in abdominopelvic malignancies. Materials and Methods: The Embase (PubMed, MEDLINE), Science Direct and IEEE Xplore Digital Library databases were searched to identify eligible studies published between Jan 2009 and March 2019. Studies that reported on the accuracy of deep learning algorithms and radiomics models for abdominopelvic malignancy by CT or MRI were selected. Study characteristics and diagnostic measures were extracted from each article. Estimates were pooled using random-effects meta-analysis. Evaluation of risk of bias was performed using the QUADAS-2 tool. Results: In total, 498 potentially eligible studies were identified, of which 21 were included and 17 offered enough information for a quantitative analysis. Studies were heterogeneous and substantial risk of bias was found in 18 studies. Almost all studies employed radiomics models (n¼20). The single published deep-learning model out-performed radiomics models with a higher AUROC (0.912 vs 0.895), but both radiomics and deep-learning models outperformed the radiologist’s interpretation in isolation (0.774). Pooled results for radiomics nomograms amongst tumour subtypes demonstrated the highest AUC 0.895 (95%CI, 0.810 - 0.980) for urological malignancy, and the lowest AUC 0.798 (95%CI, 0.744 - 0.852) for colorectal malignancy. Conclusions: Radiomics models improve the diagnostic accuracy of lymph node staging for abdominopelvic malignancies in comparison with radiologist’s assessment. Deep learning models may further improve on this, but data remain limited.
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Outcomes of open vs laparoscopic vs robotic vs transanal total mesorectal excision (TME) for rectal cancer: a network meta-analysis
(Springer, 2023) Seow, W.; Dudi-Venkata, N.N.; Bedrikovetski, S.; Kroon, H.M.; Sammour, T.
BACKGROUND: Total mesorectal excision (TME) for rectal cancer can be achieved using open (OpTME), laparoscopic (LapTME), robotic (RoTME), or transanal techniques (TaTME). However, the optimal approach for access remains controversial. The aim of this network meta-analysis was to assess operative and oncological outcomes of all four surgical techniques. METHODS: Ovid MEDLINE, EMBASE, and PubMed databases were searched systematically from inception to September 2020, for randomised controlled trials (RCTs) comparing any two TME surgical techniques. A network meta-analysis using a Bayesian random-effects framework and mixed treatment comparison was performed. Primary outcomes were the rate of clear circumferential resection margin (CRM), defined as > 1 mm from the closest tumour to the cut edge of the tissue, and completeness of mesorectal excision. Secondary outcomes included radial and distal resection margin distance, postoperative complications, locoregional recurrence, disease-free survival, and overall survival. Surface under cumulative ranking (SUCRA) was used to rank the relative effectiveness of each intervention for each outcome. The higher the SUCRA value, the higher the likelihood that the intervention is in the top rank or one of the top ranks. RESULTS: Thirty-two RCTs with a total of 6151 patients were included. Compared with OpTME, there was no difference in the rates of clear CRM: LapTME RR = 0.99 (95% (Credible interval) CrI 0.97-1.0); RoTME RR = 1.0 (95% CrI 0.96-1.1); TaTME RR = 1.0 (95% CrI 0.96-1.1). There was no difference in the rates of complete mesorectal excision: LapTME RR = 0.98 (95% CrI 0.98-1.1); RoTME RR = 1.1 (95% CrI 0.98-1.4); TaTME RR = 1.0 (95% CrI 0.91-1.2). RoTME was associated with improved distal resection margin distance compared to other techniques (SUCRA 99%). LapTME had a higher rate of conversion to open surgery when compared with RoTME: RoTME RR = 0.23 (95% CrI 0.034-0.70). Length of stay was shortest in RoTME compared to other surgical approaches: OpTME mean difference in days (MD) 3.3 (95% CrI 0.12-6.0); LapTME MD 1.7 (95% CrI - 1.1-4.4); TaTME MD 1.3 (95% CrI - 5.2-7.4). There were no differences in 5-year overall survival (LapTME HR 1.1, 95% CrI 0.74, 1.4; TaTME HR 1.7, 95% CrI 0.79, 3.4), disease-free survival rates (LapTME HR 1.1, 95% CrI 0.76, 1.4; TaTME HR 1.1, 95% CrI 0.52, 2.4), or anastomotic leakage (LapTME RR = 0.92 (95% CrI 0.63, 1.1); RoTME RR = 1.0 (95% CrI 0.48, 1.8); TaTME RR = 0.53 (95% CrI 0.19, 1.2). The overall quality of evidence as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments across all outcomes including primary and secondary outcomes was deemed low. CONCLUSIONS: In selected patients eligible for a RCT, RoTME achieved improved distal resection margin distance and a shorter length of hospital stay. No other differences were observed in oncological or recovery parameters between (OpTME), laparoscopic (LapTME), robotic (RoTME), or trans-anal TME (TaTME). However, the overall quality of evidence across all outcomes was deemed low.

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