Dileme u radioterapiji/kemoterapiji bolesnika s metastazama u limfne čvorove na vratu tumora nepoznatoga primarnog sijela

SAŽETAK Incidencija karcinoma nepoznatoga primarnog sijela s metastazama u limfne čvorove glave i vrata je niska te prema literaturi varira između 2 i 9%, te je u daljnjem padu zbog sve preciznije dijagnostike. Histološki, najčešći su planocelularni karcinomi. Osim općega fizikalnog pregleda s osobitim usmjerenjem na područje glave i vrata, nužan je endoskopski pregled s vizualizacijom nazofarinksa, orofarinksa, larinksa i hipofarinksa te radiološka slikovna obrada (CT i/ili MR te u slučaju indikacije PET/CT). Kirurško liječenje najstarija je, no još uvijek vrlo važna metoda liječenja ovih bolesnika te je preferirana opcija inicijalnog liječenja. S druge strane, primarna radioterapija predstavlja važnu opciju liječenja za tumore glave i vrata, posebno u bolesnika koji nisu kandidati za kirurško liječenje, a kod bolesnika s uznapredovalim nalazom na vratu (N2-3) preporučuje se kombinirati je s kemoterapijom. Nakon inicijalnog kirurškog liječenja i patohistološkog nalaza N2 ili N3 bolesti, radioterapija s kemoterapijom ili bez nje indicirana je u svih bolesnika, a može se razmotriti i kod onih sa statusom N1. Neovisno radi li se o primarnoj ili adjuvantnoj radioterapiji, opseg polja zračenja i nadalje je kontroverzna tema. Opcije liječenja se kreću od operativnog liječenja ipsilateralne strane vrata bez adjuvantnog liječenja, operativnog liječenja s adjuvantnom primjenom (kemo)radioterapije do primarnog liječenja – zračenja obje strane vrata i svih mjesta potencijalnog sijela primarnog tumora. Ranije je u smjernicama zagovaran agresivniji pristup koji je uključivao radioterapiju cijelog volumena ždrijela (nazofarniks, orofarinks i hipofarinks) i grkljana te obje strane vrata. S vremenom je primjetan pomak prema poštednijem liječenju, najčešće u smislu operativnog liječenja metastaza na vratu s primjenom adjuvantne ipsilateralne radioterapije, bez zračenja čitave sluznice ždrijela i grkljana. Najvažniji parametri u odluci o primjeni konkomitantne kemoterapije jesu proboj čahure limfnog čvora i resekcija R1/2

Cognitive impairment associated with chemotherapy

Rak dojke je najčešći zloćudni tumor u žena, a svaka deseta žena će ga dobiti tijekom svog života. “Post-chemotherapy cognitive impairment (PCCI)” ili „Chemotherapy related cognitive impairment (CRCI)“ je pojava kognitivnog deficita koji se javlja u otprilike trećine pacijenata nakon provedene kemoterapije. Neki od simptoma uključuju: nemogućnost obavljanja više stvari istovremeno (eng. multitasking), zbunjenost, zaboravljivost, slabo prisjećanje, iscrpljenost itd. U posljednjih 20 godina istraživanja na ovom području su ustvrdila povezanost između sistemske adjuvantne kemoterapije i kognitivnih promjena, što je potvrđeno i s nekoliko meta-analiza. Oštećenja su najčešće bila vezana uz pamćenje, izvršne funkcije, brzinu obrade informacija, orijentaciju u prostoru i verbalne sposobnosti. Iako promjene u pacijenata prema neuropsihološkim testovima mogu biti vrlo blage, one svejedno imaju snažan utjecaj na kvalitetu života. Strukturne studije su uz pomoć MR-a otkrile smanjenje gustoće sive tvari i volumena, DTI-em su otkrivene promjene cjelovitosti bijele tvari i volumena. Prozor u rad mozga su otvorile funkcionalne studije korištenjem fMR-a, koji je pokazao post-terapijske promjene u mozgu, prilikom rješavanja zadataka koji su ispitivali sjećanje i izvršne funkcije, te obrazac povezanosti mozga u odmoru. U većini slučajeva problemi s pamćenjem su privremeni, stoga je terapija usmjerena na pomaganje pacijentima da se nauče nositi sa simptomima. Razvijanje standardne terapije je otežano, obzirom da simptomi nerijetko variraju među pacijentima. Neki od pokušaja liječenja farmakoterapijskim pripravcima uključuju: metilfenidat, modafinil i donepezil.Breast cancer is the most common invasive cancer in women and one in ten women will be diagnosed during her life time. “Post – chemotherapy cognitive impairment (PCCI)” or „Chemotherapy related cognitive impairment (CRCI)“ is a phenomenon of cognitive decline that occurs approximately in one third of patients over the course of their chemotherapy. Some of the symptoms are: inability to multitask, confusion, forgetfulness, poor recall, exhaustion etc. Two decades of research, primarily in the breast cancer patient population, has confirmed an association between cognitive changes and systemic adjuvant chemotherapy as confirmed by several metaanalyses. Across cognitive studies, the specific domains affected have been relatively consistent, and include memory, executive function, processing speed, and verbal and spatial abilities. Although the changes may be relatively mild as measured by current psychometric methods, such mild cognitive dysfunction may have a very significant impact on quality of life. Structural changes detected include decreased gray matter density and volume on anatomic MRI and alteration in white matter integrity and volume on diffusion tensor imaging (DTI). fMRI studies have demonstrated post-treatment changes in brain activation during memory and executive tasks and in resting brain connectivity pattern. Developing standard therapy is difficult, given that symptoms often vary among patients. In most cases, memory problems are temporary, so the therapy is focused on helping patients to learn to cope with the symptoms. Attempts using medications include: methylphenidate, modafinil and donepezil

Cognitive impairment associated with chemotherapy

Rak dojke je najčešći zloćudni tumor u žena, a svaka deseta žena će ga dobiti tijekom svog života. “Post-chemotherapy cognitive impairment (PCCI)” ili „Chemotherapy related cognitive impairment (CRCI)“ je pojava kognitivnog deficita koji se javlja u otprilike trećine pacijenata nakon provedene kemoterapije. Neki od simptoma uključuju: nemogućnost obavljanja više stvari istovremeno (eng. multitasking), zbunjenost, zaboravljivost, slabo prisjećanje, iscrpljenost itd. U posljednjih 20 godina istraživanja na ovom području su ustvrdila povezanost između sistemske adjuvantne kemoterapije i kognitivnih promjena, što je potvrđeno i s nekoliko meta-analiza. Oštećenja su najčešće bila vezana uz pamćenje, izvršne funkcije, brzinu obrade informacija, orijentaciju u prostoru i verbalne sposobnosti. Iako promjene u pacijenata prema neuropsihološkim testovima mogu biti vrlo blage, one svejedno imaju snažan utjecaj na kvalitetu života. Strukturne studije su uz pomoć MR-a otkrile smanjenje gustoće sive tvari i volumena, DTI-em su otkrivene promjene cjelovitosti bijele tvari i volumena. Prozor u rad mozga su otvorile funkcionalne studije korištenjem fMR-a, koji je pokazao post-terapijske promjene u mozgu, prilikom rješavanja zadataka koji su ispitivali sjećanje i izvršne funkcije, te obrazac povezanosti mozga u odmoru. U većini slučajeva problemi s pamćenjem su privremeni, stoga je terapija usmjerena na pomaganje pacijentima da se nauče nositi sa simptomima. Razvijanje standardne terapije je otežano, obzirom da simptomi nerijetko variraju među pacijentima. Neki od pokušaja liječenja farmakoterapijskim pripravcima uključuju: metilfenidat, modafinil i donepezil.Breast cancer is the most common invasive cancer in women and one in ten women will be diagnosed during her life time. “Post – chemotherapy cognitive impairment (PCCI)” or „Chemotherapy related cognitive impairment (CRCI)“ is a phenomenon of cognitive decline that occurs approximately in one third of patients over the course of their chemotherapy. Some of the symptoms are: inability to multitask, confusion, forgetfulness, poor recall, exhaustion etc. Two decades of research, primarily in the breast cancer patient population, has confirmed an association between cognitive changes and systemic adjuvant chemotherapy as confirmed by several metaanalyses. Across cognitive studies, the specific domains affected have been relatively consistent, and include memory, executive function, processing speed, and verbal and spatial abilities. Although the changes may be relatively mild as measured by current psychometric methods, such mild cognitive dysfunction may have a very significant impact on quality of life. Structural changes detected include decreased gray matter density and volume on anatomic MRI and alteration in white matter integrity and volume on diffusion tensor imaging (DTI). fMRI studies have demonstrated post-treatment changes in brain activation during memory and executive tasks and in resting brain connectivity pattern. Developing standard therapy is difficult, given that symptoms often vary among patients. In most cases, memory problems are temporary, so the therapy is focused on helping patients to learn to cope with the symptoms. Attempts using medications include: methylphenidate, modafinil and donepezil

Cognitive impairment associated with chemotherapy

Rak dojke je najčešći zloćudni tumor u žena, a svaka deseta žena će ga dobiti tijekom svog života. “Post-chemotherapy cognitive impairment (PCCI)” ili „Chemotherapy related cognitive impairment (CRCI)“ je pojava kognitivnog deficita koji se javlja u otprilike trećine pacijenata nakon provedene kemoterapije. Neki od simptoma uključuju: nemogućnost obavljanja više stvari istovremeno (eng. multitasking), zbunjenost, zaboravljivost, slabo prisjećanje, iscrpljenost itd. U posljednjih 20 godina istraživanja na ovom području su ustvrdila povezanost između sistemske adjuvantne kemoterapije i kognitivnih promjena, što je potvrđeno i s nekoliko meta-analiza. Oštećenja su najčešće bila vezana uz pamćenje, izvršne funkcije, brzinu obrade informacija, orijentaciju u prostoru i verbalne sposobnosti. Iako promjene u pacijenata prema neuropsihološkim testovima mogu biti vrlo blage, one svejedno imaju snažan utjecaj na kvalitetu života. Strukturne studije su uz pomoć MR-a otkrile smanjenje gustoće sive tvari i volumena, DTI-em su otkrivene promjene cjelovitosti bijele tvari i volumena. Prozor u rad mozga su otvorile funkcionalne studije korištenjem fMR-a, koji je pokazao post-terapijske promjene u mozgu, prilikom rješavanja zadataka koji su ispitivali sjećanje i izvršne funkcije, te obrazac povezanosti mozga u odmoru. U većini slučajeva problemi s pamćenjem su privremeni, stoga je terapija usmjerena na pomaganje pacijentima da se nauče nositi sa simptomima. Razvijanje standardne terapije je otežano, obzirom da simptomi nerijetko variraju među pacijentima. Neki od pokušaja liječenja farmakoterapijskim pripravcima uključuju: metilfenidat, modafinil i donepezil.Breast cancer is the most common invasive cancer in women and one in ten women will be diagnosed during her life time. “Post – chemotherapy cognitive impairment (PCCI)” or „Chemotherapy related cognitive impairment (CRCI)“ is a phenomenon of cognitive decline that occurs approximately in one third of patients over the course of their chemotherapy. Some of the symptoms are: inability to multitask, confusion, forgetfulness, poor recall, exhaustion etc. Two decades of research, primarily in the breast cancer patient population, has confirmed an association between cognitive changes and systemic adjuvant chemotherapy as confirmed by several metaanalyses. Across cognitive studies, the specific domains affected have been relatively consistent, and include memory, executive function, processing speed, and verbal and spatial abilities. Although the changes may be relatively mild as measured by current psychometric methods, such mild cognitive dysfunction may have a very significant impact on quality of life. Structural changes detected include decreased gray matter density and volume on anatomic MRI and alteration in white matter integrity and volume on diffusion tensor imaging (DTI). fMRI studies have demonstrated post-treatment changes in brain activation during memory and executive tasks and in resting brain connectivity pattern. Developing standard therapy is difficult, given that symptoms often vary among patients. In most cases, memory problems are temporary, so the therapy is focused on helping patients to learn to cope with the symptoms. Attempts using medications include: methylphenidate, modafinil and donepezil

Dose-volume derived nomogram as a reliable predictor of radiotherapy-induced hypothyroidism in head and neck cancer patients

The aim of this study was to determine the possible predictive value of various dosimetric parameters on the development of hypothyroidism (HT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy

Dose-volume derived nomogram as a reliable predictor of radiotherapy-induced hypothyroidism in head and neck cancer patients

Background The aim of this study was to determine the possible predictive value of various dosimetric parameters on the development of hypothyroidism (HT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. ----- Patients and methods This study included 156 patients with HNSCC who were treated with (chemo)radiotherapy in a primary or postoperative setting between August 2012 and September 2017. Dose-volume parameters as well as V10 toV70, D02 to D98, and the VS10 to VS70 were evaluated. The patients’ hormone status was regularly assessed during follow-up. A nomogram (score) was constructed, and the Kaplan-Maier curves and Log-Rank test were used to demonstrate the difference in incidence of HT between cut-off values of specific variables. ----- Results After a median follow-up of 23.0 (12.0–38.5) months, 70 (44.9%) patients developed HT. In univariate analysis, VS65, Dmin, V50, and total thyroid volume (TTV) had the highest accuracy in predicting HT. In a multivariate model, HT was associated with lower TTV (OR 0.31, 95% CI 0.11–0.87, P = 0.026) and Dmin (OR 9.83, 95% CI 1.89–108.08, P = 0.042). Hypothyroidism risk score (HRS) was constructed as a regression equation and comprised TTV and Dmin. HRS had an AUC of 0.709 (95% CI 0.627–0.791). HT occurred in 13 (20.0%) patients with a score 7.1. ----- Conclusions The dose volume parameters VS65, Dmin, V50, and TTV had the highest accuracy in predicting HT. The HRS may be a useful tool in detecting patients with high risk for radiation-induced hypothyroidism