BACKGROUND: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. METHODS: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

• MeSH
• adenokarcinom farmakoterapie   mortalita   radioterapie   MeSH
• adenoskvamózní karcinom farmakoterapie   mortalita   radioterapie   MeSH
• chemoradioterapie * metody   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory děložního čípku * farmakoterapie   mortalita   radioterapie   MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• spinocelulární karcinom farmakoterapie   mortalita   radioterapie   MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

• MeSH
• adenokarcinom mortalita   patologie   patofyziologie   terapie   MeSH
• adenoskvamózní karcinom mortalita   patologie   patofyziologie   terapie   MeSH
• adjuvantní chemoterapie MeSH
• adjuvantní radioterapie MeSH
• asymptomatické nemoci MeSH
• dospělí MeSH
• hysterektomie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru mortalita   patologie   patofyziologie   terapie   MeSH
• lymfatické uzliny patologie   MeSH
• míra přežití MeSH
• multivariační analýza MeSH
• nádory děložního čípku mortalita   patologie   patofyziologie   terapie   MeSH
• neuroendokrinní karcinom mortalita   patologie   patofyziologie   terapie   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• spinocelulární karcinom mortalita   patologie   patofyziologie   terapie   MeSH
• staging nádorů MeSH
• trachelektomie MeSH
• tumor burden MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Primary lung carcinoma is an exceptionally rare childhood tumour, as per definition of the European Cooperative Study Group on Paediatric Rare Tumours (EXPeRT), with an incidence of 0.1-0.2/1,000,000 per year. Little is known about the clinical characteristics of children with primary lung carcinoma, a gap which this joint analysis of the EXPeRT group aimed to fill. PATIENTS AND METHODS: We performed a retrospective case series of children (aged 0-18 years) with primary lung carcinoma, as collected through the EXPeRT databases between 2000 and 2021. We recorded relevant clinical characteristics including treatment and outcome. RESULTS: Thirty-eight patients were identified with a median age of 12.8 years at diagnosis (range: 0-17). Mucoepidermoid carcinoma (MEC) was the most frequent entity (n = 20), followed by adenocarcinoma (n = 12), squamous cell carcinoma (n = 4), adenosquamous carcinoma (n = 1) and small-cell lung cancer (n = 1). Patients with MEC presented rarely with lymph node metastases (2/20 cases). Overall, 19/20 patients achieved long-lasting remission by surgical resection only. Patients with other histologies often presented in advanced stages (14/18 TNM stage IV). With multimodal treatment, 3-year overall survival was 52% ± 13%. While all patients with squamous cell carcinoma died, the 12 patients with adenocarcinoma had a 3-year overall survival of 64% ± 15%. CONCLUSIONS: Primary lung carcinomas rarely occur in children. While the outcome of children with MEC is favourable with surgery alone, patients with other histotypes have a poor prognosis, despite aggressive treatment, highlighting the need to develop new strategies for these children, such as mutation-guided treatment.

• MeSH
• adenokarcinom * patologie   MeSH
• adenoskvamózní karcinom * MeSH
• dítě MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• mukoepidermoidní karcinom * patologie   MeSH
• plíce patologie   MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom * patologie   MeSH
• syndrom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

• MeSH
• adenokarcinom mortalita   chirurgie   MeSH
• adenoskvamózní karcinom mortalita   chirurgie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• miniinvazivní chirurgické výkony MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory děložního čípku mortalita   chirurgie   MeSH
• přežití bez známek nemoci MeSH
• spinocelulární karcinom mortalita   chirurgie   MeSH
• trachelektomie MeSH
• zachování plodnosti MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Brazílie MeSH

• MeSH
• adenoidně cystický karcinom MeSH
• adenokarcinom MeSH
• adenoskvamózní karcinom MeSH
• gastroezofageální junkce MeSH
• lidé MeSH
• mukoepidermoidní karcinom MeSH
• nádory jícnu * klasifikace   MeSH
• neuroendokrinní karcinom MeSH
• spinocelulární karcinom klasifikace   MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• venetoklax,
• MeSH
• adenoskvamózní karcinom chirurgie   diagnostické zobrazování   sekundární   MeSH
• chronická lymfatická leukemie farmakoterapie   krev   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenopatie diagnostické zobrazování   etiologie   farmakoterapie   MeSH
• nádory plic chirurgie   diagnostické zobrazování   sekundární   MeSH
• opakovaná terapie * MeSH
• progrese nemoci MeSH
• protinádorové látky * aplikace a dávkování   MeSH
• recidiva MeSH
• rituximab aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Lung metastasis and metachronous double primary lung cancer are both common and often present diagnostic challenges. We present a case of metachronous isolated contralateral lung metastasis from pulmonary adenosquamous carcinoma with EGFR mutation. A 75-yearold woman presented with left lung nodule on a routine follow-up chest radiograph. She had had surgery for pulmonary adenocarcinoma with EGFR Ex21 L858R mutation 6 years ago. She underwent surgical resection, and histologic findings revealed adenosquamous carcinoma with the same EGFR mutation. Re-assessment of the resected specimen of the primary tumor resected 6 years ago revealed the morphologically similarity to the left lung tumor. Based on morphological and genetic identity, final diagnosis was adenosquamous cell carcinoma and metachronous isolated contralateral lung metastasis. The diagnosis of metachronous isolated metastasis is difficult but important for appropriate management and prediction of prognosis. A careful pathological examination and evaluation of genetic abnormality are needed to make the correct diagnosis.

• MeSH
• adenoskvamózní karcinom * MeSH
• diferenciální diagnóza MeSH
• erbB receptory genetika   MeSH
• lidé MeSH
• management péče o pacienta metody   MeSH
• metastázy nádorů * MeSH
• mutace MeSH
• nádory plic * MeSH
• pneumektomie metody   MeSH
• sekundární malignity * MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: To evaluate the molecular underpinnings of the rare aggressive prostate cancer variants adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma. METHODS AND RESULTS: We retrieved 19 tumours with one or more variant(s), and performed ERG immunohistochemistry, a next-generation sequencing assay targeting recurrent gene fusions, and fluorescence in-situ hybridisation (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid carcinoma (n = 10), adenosquamous carcinoma (n = 7), and pleomorphic giant-cell carcinoma (n = 7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in nine (47%, seven via sequencing, showing TMPRSS2-ERG fusions and one GRHL2-ERG fusion, and two via FISH, showing rearrangement via deletion). ERG was immunohistochemically positive in the adenocarcinoma in eight of nine (89%) patients, but was immunohistochemically positive in the variant in only five of nine patients (56%, typically decreased). One patient had a false-positive ERG immunohistochemical result in the sarcomatoid component despite a negative FISH result. Two (11%) harboured BRAF fusions (FAM131A-BRAF and SND1-BRAF). CONCLUSIONS: ERG fusions are present in these rare prostate cancer variants with a frequency close to that in conventional prostate cancer (9/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma, but is less sensitive for the variant histology, with weak to negative staining. Adenosquamous and sarcomatoid variants can, particularly, occur together. Molecular assessment may be an additional tool in selected cases to confirm the prostatic origin of unusual tumours. The presence of two BRAF rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1-2% of prostate cancers.

• MeSH
• adenoskvamózní karcinom genetika   patologie   MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• fúze genů * MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genová přestavba MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů genetika   patologie   MeSH
• nádory prostaty genetika   patologie   MeSH
• obrovskobuněčný karcinom genetika   patologie   MeSH
• protoonkogenní proteiny B-raf genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• serinové endopeptidasy genetika   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• transkripční regulátor ERG genetika   metabolismus   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Dlouhodobého přežití nemocných s časným stadiem karcinomu žaludku a gastroezofageální junkce dosahovalo pouze 25 % pacientů. Moderní multimodální přístup k léčbě těchto nádorů přežití téměř zdvojnásobil. Základním předpokladem úspěšné léčby je provedení adekvátního chirurgického resekčního výkonu v centrech, které se na tuto náročnou operativu specializují. U karcinomu žaludku se dnes jako preferovaný postup doporučuje aplikace perioperační chemoterapie. Největší efektivitu v této strategii dosahuje chemoterapeutický režim FLOT (docetaxel, oxaliplatina, fluorouracil). V případě karcinomu gastroezofageální junkce můžeme kromě perioperační chemoterapie zvolit i neoadjuvantní chemoradioterapii, která se jeví jako vhodná v případě pokročilejších tumorů, kdy je potřeba dosáhnout regrese nádoru, aby mohla být provedena resekce R0.

Gastric and gastro-oesophageal junction cancers are aggressive diseases, and only 25 % of patients with early stage disease achieve a long-term survival. The modern multimodal approach to treatment nearly doubled survival in these patients. The primary requirement for successful treatment is performing adequately radical resection in centers specialized in these challenging surgeries. In gastric cancer, the use of perioperative chemotherapy is recommended as a standard of care. The most effective regime in this approach is FLOT chemotherapy. In gastro-oesophageal junction carcinomas, in addition to perioperative therapy, neoadjuvant chemoradiotherapy appears to be appropriate strategy, mostly in cases with locally advanced carcinomas where tumor regression is required in order to perform an R0 resection

• MeSH
• adenokarcinom diagnóza   farmakoterapie   chirurgie   MeSH
• adenoskvamózní karcinom diagnóza   farmakoterapie   chirurgie   MeSH
• adjuvantní chemoterapie metody   MeSH
• chemoradioterapie metody   MeSH
• chirurgie trávicího traktu * metody   MeSH
• gastroezofageální junkce chirurgie   patofyziologie   patologie   MeSH
• gastrointestinální nádory farmakoterapie   chirurgie   terapie   MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• mezioborová komunikace MeSH
• nádory jícnu * farmakoterapie   chirurgie   terapie   MeSH
• nádory žaludku * farmakoterapie   chirurgie   terapie   MeSH
• neoadjuvantní terapie metody   MeSH
• perioperační péče metody   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVES: The aim of this study was to assess the detection rate, false-negative rate and sensitivity of SLN in LN staging in tumors over 2cm on a large cohort of patients. METHODS: Data from patients with stages pT1a - pT2 cervical cancer who underwent surgical treatment, including SLN biopsy followed by systematic pelvic lymphadenectomy, were retrospectively analyzed. A combined technique with blue dye and radiocolloid was modified in larger tumors to inject the tracer into the residual cervical stroma. RESULTS: The study included 350 patients with stages pT1a - pT2. Macrometastases, micrometastases, and isolated tumor cells were found in 10%, 8%, and 4% of cases. Bilateral detection rate was similar in subgroups with tumors<2cm, 2-3.9cm, and ≥4cm (79%, 83%, 76%) (P=0.460). There were only two cases with false-negative SLN ultrastaging for pelvic LN status among those with bilateral SLN detection. The false negative rate was very low in all three subgroups of different tumor sizes (0.9%, 0.9%, and 0.0%; P=0.999). Sensitivity reached 96% in the whole group and was high in all three groups (93%, 93%, 100%; P=0.510). CONCLUSIONS: If the tracer application technique is adjusted in larger tumors, SLN biopsy can be equally reliable in pelvic LN staging in tumors smaller and larger than 2cm. The bilateral detection rate and false negative rate did not differ in subgroups of patients with tumors<2cm, 2-3.9cm, and ≥4cm.

• MeSH
• adenokarcinom diagnóza   patologie   MeSH
• adenoskvamózní karcinom diagnóza   patologie   MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• dospělí MeSH
• falešně negativní reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie MeSH
• lymfatické metastázy MeSH
• lymfatické uzliny patologie   MeSH
• mikrometastázy MeSH
• nádory děložního čípku diagnóza   patologie   MeSH
• pánev MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• spinocelulární karcinom diagnóza   patologie   MeSH
• staging nádorů MeSH
• tumor burden MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH