IMPORTANCE: Application of deep learning algorithms to whole-slide pathology images can potentially improve diagnostic accuracy and efficiency. OBJECTIVE: Assess the performance of automated deep ...learning algorithms at detecting metastases in hematoxylin and eosin–stained tissue sections of lymph nodes of women with breast cancer and compare it with pathologists’ diagnoses in a diagnostic setting. DESIGN, SETTING, AND PARTICIPANTS: Researcher challenge competition (CAMELYON16) to develop automated solutions for detecting lymph node metastases (November 2015-November 2016). A training data set of whole-slide images from 2 centers in the Netherlands with (n = 110) and without (n = 160) nodal metastases verified by immunohistochemical staining were provided to challenge participants to build algorithms. Algorithm performance was evaluated in an independent test set of 129 whole-slide images (49 with and 80 without metastases). The same test set of corresponding glass slides was also evaluated by a panel of 11 pathologists with time constraint (WTC) from the Netherlands to ascertain likelihood of nodal metastases for each slide in a flexible 2-hour session, simulating routine pathology workflow, and by 1 pathologist without time constraint (WOTC). EXPOSURES: Deep learning algorithms submitted as part of a challenge competition or pathologist interpretation. MAIN OUTCOMES AND MEASURES: The presence of specific metastatic foci and the absence vs presence of lymph node metastasis in a slide or image using receiver operating characteristic curve analysis. The 11 pathologists participating in the simulation exercise rated their diagnostic confidence as definitely normal, probably normal, equivocal, probably tumor, or definitely tumor. RESULTS: The area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.556 to 0.994. The top-performing algorithm achieved a lesion-level, true-positive fraction comparable with that of the pathologist WOTC (72.4% 95% CI, 64.3%-80.4%) at a mean of 0.0125 false-positives per normal whole-slide image. For the whole-slide image classification task, the best algorithm (AUC, 0.994 95% CI, 0.983-0.999) performed significantly better than the pathologists WTC in a diagnostic simulation (mean AUC, 0.810 range, 0.738-0.884; P < .001). The top 5 algorithms had a mean AUC that was comparable with the pathologist interpreting the slides in the absence of time constraints (mean AUC, 0.960 range, 0.923-0.994 for the top 5 algorithms vs 0.966 95% CI, 0.927-0.998 for the pathologist WOTC). CONCLUSIONS AND RELEVANCE: In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting.
Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available.
To determine the safety and ...feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response.
In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo.
A single fraction of 20-Gy SABR to each lesion.
Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval CI: 91–100) and 93% (95% CI: 84–100), and DPFS was 58% (95% CI: 43–77) and 39% (95% CI: 25–60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm.
A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy.
This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.
For patients with one to three oligometastases from prostate cancer, single fraction 20-Gy stereotactic ablative body radiotherapy was both safe and feasible. Local and distant progression-free survival at 2 yr were 93% and 39%, respectively. Quality of life was maintained at baseline levels using this treatment strategy.
Mechanisms of lymphatic metastasis Karaman, Sinem; Detmar, Michael
The Journal of clinical investigation,
03/2014, Letnik:
124, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Malignant tumors release growth factors such as VEGF-C to induce lymphatic vessel expansion (lymphangiogenesis) in primary tumors and in draining sentinel LNs, thereby promoting LN metastasis. ...Surprising recent evidence suggests that lymphatic vessels do not merely represent passive channels for tumor spread, but that they may actively promote tumor cell recruitment to LNs, cancer stem cell survival, and immune modulation. New imaging approaches allow the sensitive visualization of the earliest LN metastases and the quantitative, noninvasive measurement of the function of tumor-draining lymphatic vessels, with potential applications in the development of biomarkers for prognosis and measurement of therapeutic response.
Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the ...relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC.
•serum MALAT-1 contained in exosomes is upregulated in NSCLC patients.•Exosomal MALAT-1 was positively associated with TNM stage and lymphatic node metastasis.•MALAT-1 knockdown inhibited cell proliferation, colony formation and cell migration.•MALAT-1 knockdown induced cell cycle arrest and cell apoptosis.
Abstract Background Clinical trials evaluating the benefit of pelvic radiotherapy (PRT) in the radiotherapeutic management of patients with higher-risk prostate cancer have limited the superior field ...border to the S1/S2 or L5/S1 interspace. However, imaging and surgical series have demonstrated a high frequency of prostatic lymph node (LN) drainage beyond these landmarks. Objective To determine the patterns of radiographically defined abdominopelvic LN failures and their potential implications for PRT field design. Design, setting, and participants During 1992–2008, 2694 patients with localized prostate cancer were treated with prostate/seminal vesicle–only radiotherapy without PRT. Some 156 patients had their first failure within the abdominopelvic LNs, of whom 60 had isolated failures within the pelvic LNs. Outcome measurements and statistical analysis A radiologist reviewed all imaging and mapped each LN failure to a template consisting of 34 abdominopelvic LN stations. Results and limitations The median follow-up was 8.9 yr. Of patients who experienced first recurrence in the pelvic LNs ( n = 60), the common iliac station was involved in 55% ( n = 33) of patients, including 10% ( n = 6) who had isolated common iliac failures. Use of a PRT field superior border of L5/S1 would fully cover only 42% of the first recurrences among these patients. Extending the field to cover the common iliac stations would increase coverage to 93% of recurrences. The presence of T3/T4 disease and omission of androgen-deprivation therapy both independently conferred an approximate fivefold increase in the likelihood of having a common iliac LN failure. Use of imaging as a surrogate for LN involvement is the primary study limitation. Conclusions Pelvic LN failures frequently occur superior to the commonly used L5/S1 landmark for PRT coverage, and use of ADT may be protective of more superior LN failures. The current RTOG 0924 trial is evaluating the benefit of PRT with extended superior coverage to L4/5 when possible, which, according to our data, should significantly improve the coverage of potential sites of failure. Patient summary We looked at lymph node recurrence patterns after external beam radiotherapy of the prostate in men who did not have their lymph nodes treated. We found that there was a high incidence of pelvic lymph node recurrences above the internal and external iliac lymph node regions. Therefore, the current field recommendation for pelvic lymph nodes that stops at the superior border of the internal and external iliac vessels provides inadequate coverage of common sites of cancer recurrence, namely the common iliac lymph nodes.
Abstract
Background
In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be ...improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes.
Methods
Patients with low cT3–4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response.
Results
More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease.
Conclusion
Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.
Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.
This multicentre retrospective cohort study, including 1216 patients with low cT3–4 rectal cancer, demonstrated that internal iliac lateral lymph node enlargement is associated with an increased rate of lateral local recurrence, whereas obturator nodes are associated with more advanced disease resulting in increased distant metastasis and reduced cancer-specific survival rates. Lateral lymph node dissection improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.
Revised FIGO staging for carcinoma of the cervix uteri Bhatla, Neerja; Berek, Jonathan S.; Cuello Fredes, Mauricio ...
International journal of gynecology and obstetrics,
April 2019, Letnik:
145, Številka:
1
Journal Article
Recenzirano
Objective
To revise FIGO staging of carcinoma of the cervix uteri, allowing incorporation of imaging and/or pathological findings, and clinical assessment of tumor size and disease extent.
Methods
...Review of literature and consensus view of the FIGO Gynecologic Oncology Committee and related societies and organizations.
Results
In stage I, revision of the definition of microinvasion and lesion size as follows. Stage IA: lateral extension measurement is removed; stage IB has three subgroups—stage IB1: invasive carcinomas ≥5 mm and <2 cm in greatest diameter; stage IB2: tumors 2–4 cm; stage IB3: tumors ≥4 cm. Imaging or pathology findings may be used to assess retroperitoneal lymph nodes; if metastatic, the case is assigned stage IIIC; if only pelvic lymph nodes, the case is assigned stage IIIC1; if para‐aortic nodes are involved, the case is assigned stage IIIC2. Notations ‘r’ and ‘p’ will indicate the method used to derive the stage—i.e., imaging or pathology, respectively—and should be recorded. Routine investigations and other methods (e.g., examination under anesthesia, cystoscopy, proctoscopy, etc.) are not mandatory and are to be recommended based on clinical findings and standard of care.
Conclusion
The revised cervical cancer staging is applicable to all resource levels. Data collection and publication will inform future revisions.
The 2018 FIGO cervical cancer staging system allows use of imaging/pathology for stage allocation, and increases subgroups in stages I and III.
Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using ...prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management.
In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358.
From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23–31) greater accuracy than that of conventional imaging (92% 88–95 vs 65% 60–69; p<0·0001). We found a lower sensitivity (38% 24–52 vs 85% 74–96) and specificity (91% 85–97 vs 98% 95–100) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% 32% absolute difference; 28–35 for patients with pelvic nodal metastases, and 95% vs 74% 22% absolute difference; 18–26 for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 15% men 10–22 vs 41 28% men 21–36; p=0·008) and had more equivocal findings (23% 17–31 vs 7% 4–13) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8–12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT.
PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.
Movember and Prostate Cancer Foundation of Australia.
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Malignant tumors of ectodermal or endodermal origin may metastasize to the sentinel lymph node, the first lymph node encountered by tumor cells that enter lymphatics in the organ of origin. This ...pathway is enabled by the anatomy of the disease and the causes of metastasis are the result of complex interactions that include mechanical forces within the tumor and host tissues, and molecular factors initiated by tumor cell proliferation, elaboration of cytokines and changes in the tumor microenvironment. Mechanical stresses may influence complex biochemical, genetic and other molecular events and enhance the likelihood of metastasis. This paper summarizes our understanding of interacting molecular, anatomical and mechanical processes which facilitate metastasis to SLNs. Our understanding of these interacting events is based on a combination of clinical and basic science research, in vitro and in vivo, including studies in lymphatic embryology, anatomy, micro-anatomy, pathology, physiology, molecular biology and mechanobiology. The presence of metastatic tumor in the SLN is now more accurately identifiable and, based upon prospective clinical trials, paradigm-changing SLN biopsy has become the standard of clinical practice in breast cancer and melanoma.
In response to Park, et al van Diessen, Judi N.A.; Kwint, Margriet H.; Sonke, Jan-Jakob ...
Radiotherapy and oncology,
June 2020, 2020-06-00, 20200601, Letnik:
147
Journal Article
PDF
