Background: Trastuzumab significantly improves outcomes in early HER2-positive breast cancer, irrespectively of any prognostic or predictive factors. Unfortunately, about a quarter of patients ...receiving neoadjuvant trastuzumab experience disease recurrence, revealing the unquestionable need for further improvement of treatment outcomes. Summary: Adding HER2 blockade to adjuvant trastuzumab with pertuzumab and neratinib improves invasive disease-free survival (IDFS), particularly for those at highest risk of recurrence. A shift toward a neoadjuvant strategy for patients with a higher risk of recurrence could result in further treatment optimization. For patients without a pathological complete response (pCR) after the neoadjuvant part of the therapy, a switch to adjuvant trastuzumab emtansine significantly improves IDFS and distant recurrence-free survival and shows a trend towards improved overall survival (OS). On the other hand, for low-risk patients, chemotherapy deescalation should be strongly considered with the use of trastuzumab monotherapy as an anti-HER2 backbone. Key Messages: Neoadjuvant therapy should be offered for a significant proportion of HER2-positive early breast cancer patients with a higher risk of recurrence. Postneoadjuvant treatment should be tailored according to the initial stage of disease and the response to neoadjuvant treatment.
Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of ...markers predicting the response to chemotherapy might help select eligible patients and spare non-responding patients from treatment-associated toxicity. Cancer/testis antigens (CTAs) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets for cancer immunotherapies. We analyzed the correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at the protein level and the effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. The correlation between the expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria and platinum sensitivity, measured as platinum-free interval (PFI), progression free (PFS), and overall survival (OS) was explored. The MAGE-A10 protein expression predicted unresponsiveness to platinum-based chemotherapy (p = 0.005), poor platinum sensitivity (p < 0.001), poor PFS (p < 0.001), and OS (p < 0.001). Multivariate analysis identified MAGE-A10 protein expression as an independent predictor of poor platinum sensitivity (p = 0.005) and shorter OS (p < 0.001). Instead, no correlation was observed between the NY-ESO-1 protein expression and response to platinum-based chemotherapy (p = 0.832), platinum sensitivity (p = 0.168), PFS (p = 0.126), and OS (p = 0.335). The MAGE-A10 protein expression reliably identified advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted immunotherapy could represent an important alternative therapeutic option in these cancers.
Small cell neuroendocrine carcinoma of the cervix (SCNCC) is considered to be an extremely rare, highly invasive and aggressive subtype of squamous cell carcinoma. It is particulary rare during ...pregnancy. Here we report a case in which a 32-year-old patient who was admitted to our Department at 27 completed weeks of gestation with intermittent vaginal spotting and a large amount of malodorous vaginal discharge. Gynecological examination revealed a 2 cm exophytic polypoid tumor coming out of the cervix. On rectal examination there was no clinically evident parametrial invasion. Biopsy of the cervix was performed and the diagnosis of small cell neuroendocrine carcinoma was established. We reviewed and discussed the features, diagnosis, treatment and prognosis of SCNCC diagnosed during pregnancy.
Sitnostanični neuroendokrini rak cerviksa je iznimno rijedak, visoko invazivan i agresivan podtip pločastog raka cerviksa. Poglavito je rijedak tijekom trudnoće. U ovom radu prikazujemo slučaj 32- godišnje bolesnice koja je zaprimljena u našu kliniku s navršenih 27 tjedana trudnoće, s oskudnim vaginalnim krvarenjem, te obilnim iscjetkom neugodnog mirisa. Pregledom u spekulima smo pronašli polipoidnu tvorbu veličine 2 cm koja je prominirala iz cerviksa. Rektalnim pregledom nismo pronašli zahvaćenost parametrija. Učinjena je biopsija polipoidne tvorbe i postavljena dijagnoza sitnostaničnog neuroendokrinog raka cerviksa. U prikazu slučaja raspravljamo o značajkama, dijagnozi, liječenju i prognozi ovoga raka dijagnosticiranog tijekom trudnoće
Locally advanced cervical cancer (LACC) is one of the leading health problems of the developing countries. We present long-term outcomes of treatment with a concomitant chemobrachyradiotherapy ...followed by consolidation chemotherapy regimen.
We treated 118 patients with LACC (International Federation of Gynecology and Obstetrics stages IB2-IVA) with external radiotherapy (50 Gy in 25 fractions) and concomitant chemobrachyradiotherapy (low-dose rate). Chemotherapy was applied during brachyradiotherapy (cisplatin on day 1 in combination with 24-hour infusion of ifosfamide and mesna uroprotection). Four cycles of consolidation chemotherapy were given starting 4 weeks after the second concomitant chemobrachyradiotherapy cycle.
After median follow-up period of 99.3 months, we observed acceptable acute and late toxicity, local control rate of 97.5%, and an overall survival of 74.6% at 96 months.
Chemobrachyradiotherapy regimen followed by consolidation chemotherapy described in this article is a valuable treatment option for LACC.
Background
Our objective was to assess the effects of COVID‐19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers ...in the Republic of Croatia.
Subjects, Materials, and Methods
We performed a retrospective, population‐ and registry‐based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases.
Results
The average monthly percent change after the initial lockdown measures were introduced was −11.0% (95% confidence interval − 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017–2019.
Conclusion
It seems that national health care system measures for controlling the spread of COVID‐19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID‐19 control measures were relaxed, and it has not reoccurred during the second COVID‐19 wave. Although the COVID‐19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020.
Implications for Practice
It is possible to compensate for the adverse effects of COVID‐19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non‐negligible extent.
This article assesses the effects of COVID‐19 on the number of newly diagnosed breast cancer patients in the Republic of Croatia.
The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy. In the majority of patients with LACC after properly executed concomitant chemoradiotherapy local ...control of the disease is achieved, and consequently distant relapse becomes the main cause of death for these patients. In an attempt to improve the outcome of patients with LACC, we designed a regimen of concomitant chemobrachyradiotherapy with cisplatin and ifosfamide followed by consolidation chemotherapy.
Between 1999 and 2012, 118 patients diagnosed with LACC, The International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IVA, regardless of histology, were treated with concomitant chemobrachyradiotherapy and consolidation chemotherapy at our Institution. Chemotherapy consisted of two cycles of cisplatin and ifosfamide applied concomitantly with two intracavitary low-dose rate brachytherapy applications, and of four cycles of the same drug combination as an adjuvant/consolidation part of the treatment. The primary outcome in this analysis was distant disease-specific survival.
A total of 18 patients had documented relapse of cervical cancer, with only three local recurrences observed; 15 patients developed only distant recurrence, and one patient developed both local and distant recurrence. The distant disease-specific survival after a median follow-up of 96 months was 86.4%.
Consolidation or adjuvant chemotherapy that follows concomitant chemoradiotherapy has a potential role in further improving control of the disease, especially distant control of the disease.
Primjena inhibitora CDK4/6 u liječenju hormonski ovisnoga metastatskog raka dojke negativnog na HER-2 dovela je do bitnog poboljšanja kontrole bolesti, i to ponajprije znatnim produljenjem ...preživljenja bez progresije bolesti, uz prihvatljiv profil toksičnosti. Osnovno djelovanje inhibitora CDK4/6 jest odgađanje razvoja rezistencije na endokrinu terapiju, odnosno reverziju već nastale rezistencije. Medijani preživljenja bez progresije bolesti kreću se oko 20 i više mjeseci u prvoj liniji liječenja i 10-ak mjeseci i više u drugoj liniji.
U prvoj liniji liječenja kombinirani su s aromataznim inhibitorima, a u drugoj s fulvestrantom. Produljenjem vremena bez napredovanja bolesti odgađa se primjena kemoterapije, a bolesnicama se osigurava bolja
kvaliteta života. Zbog svega navedenoga ovi lijekovi u kombinaciji s endokrinom terapijom nova su, visokovrijedna terapijska opcija u liječenju metastatskog raka dojke. Međutim, ostaju brojna otvorena pitanja za svakodnevnu kliničku praksu kao što su optimalan odabir bolesnica za prvolinijsko i drugolinijsko liječenje, sekvenciranje drugih lijekova nakon progresije bolesti na inhibitore CDK4/6 te dostupnost i cijena liječenja.
Rak jajnika i jajovoda, odnosno adneksa, i primarni rak potrbušnice jest šesta po učestalosti zloćudna bolest žena i najsmrtonosniji ginekološki tumor u Hrvatskoj. Histološki je rak jajnika, jajovoda ...i potrbušnice najčešće epitelnog podrijetla, i to seroznog podtipa. Rjeđi su različiti neepitelni tumori jajnika kao i presadnice u jajnike. Posebnu skupinu čine karcinomi niskog zloćudnog potencijala označeni neinvazivnošću, klinički indolentnim tijekom i dobrom prognozom. Klinički su karcinomi u ranim stadijima razvoja uglavnom asimptomatski, tako da se najčešće dijagnosticiraju u kasnijim, uznapredovalim stadijima bolesti. Dijagnoza se potvrđuje patohistološkim nalazom, a iznimno nalazom citološkog bloka nakon provedene dijagnostičke obrade. O liječenju i praćenju bolesnica odlučuje multidisciplinarni tim uzimajući u obzir osobitosti bolesnice (dob, opće stanje i komorbiditete) kao i obilježja samog tumora (stadij bolesti, histološki tip i stupanj zloćudnosti tumora, status homologne rekombinacije, odnosno gena BRCA 1 i 2 kao i odgovor na prethodno liječenje i popratnu toksičnost ako se radi o povratu bolesti). Liječenje primarnog raka jajnika, jajovoda i potrbušnice temelji se na kirurškom liječenju, sistemskoj primjeni kemoterapije, imunoterapije, ciljane terapije i hormonske terapije kao i suportivno-simptomatskih mjera tijekom cijelog liječenja. Terapijski pristup se razlikuje kod rjeđih neepitelnih histoloških tipova ovih tumora jer se češće dijagnosticiraju u ranim stadijima bolesti, imaju indolentniji tijek, drugačiju biologiju bolesti kao i osjetljivost na sistemsko liječenje. U tekstu koji slijedi predstavljene su obnovljene i nadopunjene kliničke upute s ciljem standardizacije postupaka i kriterija postavljanja dijagnoze, liječenja te praćenja bolesnica s rakom jajnika, jajovoda i potrbušnice u Hrvatskoj. Prvo izdanje smjernica za dijagnozu, liječenje i praćenje bolesnica s rakom jajnika objavljeno je 2013. godine.1
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