Narrow-band imaging vs Lugol chromoendoscopy in screening for esophageal squamous cell neoplasia: a randomized trial.

INTRODUCTION: To date, there is no established optimal method for endoscopic detection of esophageal squamous cell neoplasia in high­risk individuals. OBJECTIVES: We aimed to compare the performance of narrow­band imaging (NBI) and Lugol chromoendoscopy in screening for esophageal neoplasia among patients with a history of treatment for head and neck squamous cell cancer (HNSCC). PATIENTS AND METHODS: We randomly assigned 300 patients who had completed curative treatment for HNSCC at least 1 year prior to the inclusion to undergo either NBI or Lugol endoscopy (2:1 ratio). Following white­light examination of the esophagus, the assigned imaging study was performed, and biopsies were taken from any suspicious lesions identified using NBI or Lugol chromoendoscopy. The primary end point was positive predictive value (PPV) of the biopsied lesion for a diagnosis of esophageal neoplasia (high­grade intraepithelial neoplasia [HG­IEN] or invasive esophageal squamous cell carcinoma [ESCC]). The secondary end points included the number of biopsied lesions, duration of esophagus examination, and endoscopy tolerance. RESULTS: In 294 patients included in the final analysis (NBI, n = 204; Lugol chromoendoscopy, n = 90), we diagnosed 3 ESCCs (1.02%) and 2 HG­IENs (0.68%). The PPV of NBI and Lugol chromoendoscopy in per­lesion analysis was 7.69% (95% CI, 0.94%-25.1%) and 8.11% (95% CI, 1.7%-21.9%), respectively (P >0.99). NBI outperformed Lugol chromoendoscopy in terms of the rate of patients requiring biopsy (12.75% vs 41.11%; P = 0.003), duration of esophagus examination (3.5 min vs 5.15 min; P <0.001), and endoscopy tolerance assessed on the visual analog scale (25 mm vs 36.5 mm; P = 0.002). CONCLUSIONS: With a PPV comparable to that of Lugol chromoendoscopy, but a lower number of biopsies required, shorter examination time, and better patient tolerance, NBI could be considered the primary screening method for ESCC in patients with HNSCC.

Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651.

PURPOSE: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations. RESULTS: Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME. CONCLUSION: CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.

Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych doroslych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022].

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

Nutritional Care in Patients with Head and Neck Cancer during Chemoradiotherapy (CRT) and Bioradiotherapy (BRT) Provides Better Compliance with the Treatment Plan.

The treatment of locally advanced head and neck cancer (HNC) is based on extensive resections followed by concurrent chemoradiotherapy (CRT) with platinum derivatives or concurrent radiotherapy with cetuximab (bioradiotherapy; BRT). Malnutrition, which occurs in up to 60% of patients before treatment commencement, severely increases the risk of CRT/BRT drug dose reductions and the incidence of treatment-related adverse events. A prospective observational study was performed regarding the influence of nutritional care on nutritional status, compliance with the treatment's planned regimen, and the incidence of treatment-related complications in patients with advanced HNC during CRT and BRT. The study population encompassed 153 patients compared with a retrospective control group of 72 patients treated before nutritional care was included in the standard of oncological care. Patients enrolled in the nutritional care programme received significantly higher doses of platinum derivatives or cetuximab than patients in the control group. A significant difference between the compared populations was observed in patients below 70 years of age (92.8% of the study population), after prior surgery, and with initial weight loss lower than 10%. Nutritional care reduced final weight loss and prevented a decline within the laboratory markers of nutritional status. Weight loss was comparable in both modes of treatment-CRT and BRT. The incidence of treatment-related complications was significantly higher in patients without nutritional support in the subgroups of patients under 70 years of age and after primary surgery. Nutritional care before and during CRT and BRT in patients with HNC is a determinant of therapeutic benefit, defined as preventing down-dosing, weight loss, and the incidence of complications. Platinum derivatives and cetuximab had comparable influence on weight loss.

Recurrence of adenoid cystic carcinoma of the trachea treated with radical radiotherapy: A case report.

Adenoid cystic carcinoma (ACC) of the trachea is a relatively rare tumor among thoracic diseases. The present study reports the case of a 23-year-old woman with ACC of the trachea who underwent surgical resection of the tumor in The National Institute of Tuberculosis and Lung Diseases (Warsaw, Poland). Histopathological examination revealed that the tumor was not completely resected (R2 resection) and strict observation of the patient was therefore prescribed. After ~9 years of follow-up, clinical and histopathological tumor progression was confirmed and the patient was referred to the Centre of Oncology in Warsaw. The localization and advanced nature of the disease precluded surgical intervention, and radical radiotherapy was therefore performed using intensity-modulated radiation therapy. A total dose of 7,590 Gy, the planning target volume, was administered. A hyperfractionation scheme of radiotherapy was used: 2 fractions of 1.15 Gy daily, with at least a 6 h break in between. Tumor regression was observed following treatment and has been maintained for >3 years, assessed by clinical and computed tomography and positron emission tomography imaging examinations.

Comparative analysis of the incidence of head and neck cancer in south-eastern Poland and in Poland in the years 1990-2012.

AIM OF THE STUDY: To present the changes in the incidence of cancers of the head and neck organs in south-eastern Poland and in the whole country in the years 1990-2012. MATERIAL AND METHODS: A retrospective analysis the incidence of cancers of the head and neck organs in south-eastern Poland in the years 1990-2012. Statistical methods used for cancers of ICD-10 C00-C14 and C30-C32. RESULTS: For Poland, the absolute number of cases was 123,120 in the years 1990-2012. For males, the number of cases per year increased from 4468 in 1990 to 4953 in 2012, and for females from 816 to 1442. The percentage share of tumours of the head and neck in all malignant tumours decreased from 10.0% to 6.5% for males and from 2.1% to 1.9% for females. In the years 1990-2012 in south-eastern Poland, for males, the absolute number of cases per year decreased from 335 in 1990 to 286 in 2012. For females, a minimal increase in cases was from 63 to 64 cases. The percentage share of tumours of the head and neck in all malignant tumours decreased from 12.2% to 6.7% for males and from 2.7% to 1.8% for females. CONCLUSIONS: Incidences of cancers of the head and neck organs in Poland have seen a slight upward trend in the absolute number of cases over the last two decades. In Poland a decrease in the incidence of cancer of the larynx was reported, with an increase in the incidence of oropharyngeal cancer.

Hypofractionated accelerated radiotherapy in T1-3 N0 cancer of the larynx: A prospective cohort study with historical controls.

AIM: The goal of this prospective study was to assess the effectiveness of a hypofractionated accelerated regime in treatment of the larynx cancer. BACKGROUND: Multiple radiotherapy delivery regimes are used for treatment of the larynx cancer. Hypofractionated regimes could provide similar results with reduced use of radiotherapy facilities. MATERIAL AND METHODS: 223 patients with squamous cell carcinoma of the upper or middle larynx have been treated with 63 Gy delivered in 28 fractions of 2.25 Gy during 38 days, 5 fractions per week. The study endpoints were overall survival, progression-free survival, early and late treatment toxicity. Standard and accelerated radiotherapy groups from the study published by Hliniak et al.20 served as controls. RESULTS: Five-year actuarial overall survival was 87.5% in the study group, 84.5% in the control group receiving accelerated radiotherapy (33 fractions of 2.0 Gy, 6 fractions per week) and 86.2% in the control group (33 fractions of 2.0 Gy, 5 fractions per week). Five-year progression-free survival was 73.6%, 77.2% and 66.2%, respectively. Overall, treatment toxicity and complication rates did not differ between the study group and the control groups. CONCLUSIONS: The hypofractionated accelerated radiotherapy protocol using 5 fractions per week reduced the use of radiotherapy facilities. There was no significant difference in overall survival and progression-free survival between the study and control groups treated with accelerated or standard radiotherapy.

Evaluation of efficacy of Caphosol in prevention and alleviation of acute side effects in patients treated with radiotherapy for head and neck cancers.

AIM OF THE STUDY: Oral mucositis is a common side effect of the oral mucosa due to anticancer therapy, especially for head and neck cancer. Caphosol is indicated for dryness of the mouth and oropharynx and treatment of mucositis due to irradiation or high-dose chemotherapy. The aim of the study was to evaluate the efficacy of Caphosol in preventing and alleviating mucositis due to radiotherapy in the head and neck region. MATERIAL AND METHODS: Caphosol was used from the beginning of the irradiation and for two weeks more after the treatment was completed. Mucositis, xerostomia, and dysphagia were scored by radiotherapists. Subjective evaluation was made by patients. Caphosol was assessed in a non-blinded, matched clinical study. Each treatment arm consisted of 50 patients. The groups were similar. The only difference in the management protocol between the treatment arms was the use of Caphosol in the experimental arm. RESULTS: A statistically significant difference in mean severity of early irradiation-induced side effects between the studied groups was observed with respect to: mucositis in the clinical target volume (CTV) area, mucositis in the increased dose (boost) area, dysphagia and xerostomia (p < 0.001 for all reactions). In the group of patients who used Caphosol, the mucositis was less intense, both in the CTV and in the boost area. CONCLUSIONS: The use of Caphosol reduces the severity of acute mucositis, dysphagia and xerostomia, exerting a positive effect on comfort in the oral cavity in patients irradiated for head and neck tumors.

Usefulness of Somatostatin Receptor Scintigraphy (Tc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography.

AIMS: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. METHODS: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. RESULTS: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). CONCLUSION: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

[Long-term results and cause of failure analysis in larynx cancer patients irradiated conventionally and with accelerated fractionation schedules in 1995-1998]. / Odlegle wyniki i analiza przyczyn niepowodzen u chorych na raka krtani napromienianych konwencjonalnie i schematem przyspieszonego frakcjonowania w latach 1995-1998.

The clinical material consists of 217 patients with squamous cell carcinoma in supraglottic and glottic larynx in clinical stage T1-3N0M0 irradiated radically in Warsaw Oncology Centre in 1995-1998. All patients were treated with Co-60, according to two schedules of fractionation, with maintenance of the consistent therapeutic protocol. The same team of doctors worked on the treatment of patients and on the follow-up as well. The clinical material is a part of a three-phased clinical trial KBN 0295. In the course of observation, the progression of cancer was not observed in 157 patients, among whom, 66% were treated conventionally and 79% with accelerated fractionation method. 60 cases of loco-regional recurrences were noted, among which 55 were regional. The majority of failure cases was observed until the 30(th) of the month after the radiotherapy ended. In conventional fractionation treatment, recurrences in T1 were 8/31 (26%), in T2 22/59 (37%) and in T3 8/20 (40%). In patients treated with AF, recurrences were T1 5/39 (13%), T2 15/55 (27%) and T3 2/13 (15%) respectively. The percentage of primary site tumour recurrences for each localization and kind of treatment was analysed. In CF 28/78 (37%) of glottic tumour recurrences and 10/34 (29%) of supraglottic tumour, recurrences were observed. In AF, 12/71 (17%) and 10/36 (28%) were observed respectively. In 48 cases salvage surgery was used, and 12 patients were not qualified because of tumour massive progression or because they refused to have a surgery. Among 34 cases (16%) of the second primary tumour or distant methastases, 25 were observed with glottic cancer, among which 23 were observed in early stages, and 9 cases with supraglottic cancer, among which, 6 showed early stage of tumour. In only 3 cases out of all the patients, distant methastases were confirmed in histopatology examination. The main cause of failure in larynx cancer patients in stage T1 is that 3N0M0 are local recurrences. Second primary or distant methastases constitute 16% of the patients in this paper.

Follow-up in patients treated for head and neck cancer.

Principles of follow-up management in patients treated for head and neck tumors are not very strictly defined, and practice varies between countries, centers, and specialists. Details of follow-up procedures, including timing of outpatient visits and diagnostic imaging, are specific for tumor types and localizations but also depend on treatment modalities used, availability of diagnostic procedures, and socioeconomic factors. The authors describe general principles of follow-up in head and neck cancer patients. Clinical observation and laboratory and imaging studies in patients who had received radical treatment should focus on early identification of recurrent or second primary tumors to allow for a salvage radical therapy. In patients who initially had received a palliative care, the follow-up should focus on proper management of symptoms.

Tracheal adenoid cystic carcinoma mimicking a thyroid tumor: A case report.

At present, only eight cases of tracheal adenoid cystic carcinomas (ACCs) mimicking thyroid tumors have been reported. Since there are no guidelines available regarding their diagnosis and treatment, they present a significant clinical challenge. In the present study, patient treatment was analyzed to deliver the first concise summary of treatment options in patients with ACC mimicking a thyroid tumor. In addition, all available data regarding molecular abnormalities of this disease have been discussed. The current study presents a case of a 17-year-old patient with a tracheal ACC mimicking a thyroid tumor. The patient was diagnosed in 2007 with a pathological mass between the left lobe of the thyroid and the trachea, and underwent surgery and radiotherapy. In 2010, multiple lesions in the lungs were diagnosed and pulmonary metastasectomy was performed. Following surgery, the patient has been disease-free for almost 30 months. Thyroid tumor biopsy may reveal ACCs. This pathological report requires further investigation of the head and neck in order to confirm if the disease is of tracheal origin. Patients may present with a neck swelling, hoarseness of voice or dysphagia. Surgery must be considered as first-line therapy for all patients with local disease as it may be curative. For palliative treatment chemoradiotherapy based on cisplatin may be effective. The identification of cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations and mitochondrial abnormalities specific for ACCs is critical to the development of targeted therapies. Thus far, large studies have only reported the transcriptional activator Myb and mammalian target of rapamycin signaling pathway to be disrupted in ACCs.

[The results and toxicity of organ preservation treatment for locoregionally advanced laryngeal and hypopharyngeal cancer]. / Ocena wyników i tolerancji zachowawczego leczenia oszczedzajacego narzad u chorych na lokoregionalnie zaawansowanego raka krtani i krtaniowej czesci gardla.

UNLABELLED: The most frequent malignant tumor of the head and neck region is a squamous cell cancer of the larynx. Squamous cell cancer of the hypopharynx is diagnosed rarely, but it has poorer prognosis than laryngeal cancer. The surgical treatment, especially in advanced disease, is a laryngectomy with the definitive tracheostomy, what negatively influenced the quality of life. Therefore, oncologists have been interested in new alternative methods of conservative treatment from many years. THE AIM OF THE STUDY: The evaluation of efficacy and toxicity of the organ preservation treatment in patients with locally advanced laryngeal and hypopharyngeal cancer. MATERIAL AND METHODS: The patients with diagnosed squamous cell laryngeal and hypopharyngeal cancer in III and IVa clinical status were treated with concomitant radiochemotherapy with intention of the organ preservation. Conformal 3D radiotherapy and SIB-IMRT technique was applied in all cases. Concomitant chemotherapy consisted of cisplatin in daily dose100mg/m(2) given two times during irradiation (1 and 22 day of treatment) or once weekly in dose 40mg/m(2). Between January 2004 and November 2008 146 patients were treated with this method. There were 83 patients diagnosed with laryngeal cancer and 62 patients with hypopharyngeal cancer in this group. RESULTS: The median follow up is 42 months. Five years overall survival is 75% and disease free survivak is 63%. Three years laryngectomy free survival (LFS) is 82% and 5-years LFS is 76%. This group of patients is alive with larynx preservations. In 17.3% patients local recurrence was observed (4.5% regional recurrence and 1.8% locoregional). Those patients underwent salvage surgery or were treated with palliative chemotherapy. No severe life risking early and late complications were observed. Only 7% of patients have required temporary tracheostomy because of difficulties in breathing due to larynx edema. CONCLUSION: We can conclude that organ preservation treatment is a valuable alternative to surgical procedure in patients diagnosed with laryngeal and hypopharyngeal cancer in III and IVa clinical status.

[The results of combined treatment patients with olfactory neuroblastoma in material of Cancer Center in Warsaw]. / Wyniki skojarzonego leczenia nerwiaka wechowego (olfactory neuroblastoma) w materiale Centrum Onkologii w Warszawie.

UNLABELLED: The results of combined treatment patients with olfactory neuroblastoma in material of Cancer Center in Warsaw AIM: The analysis of the results of combined treatment patients with olfactory neuroblastoma in material of Cancer Center in Warsaw. MATERIAL: Authors present material of 27 cases olfactory neuroblastoma treated in Cancer Center of Warsaw from 1965 to 2008. The median age was 44 years (range 10-74). The median observation was 72 months (range 2-235).The tumors were seen in 15 women and 12 men. According to Kadish staging there were one A, eight B, and seventeen C stage tumor. The patients in stage A and B was treated by surgery and radiotherapy (mean dose in whole material was 57.15 Gy range 44-70). Five patients in stage C was treated by surgery, radiotherapy and adjuvant chemotherapy. Five patients were treated by neoadjuvant chemotherapy and radiotherapy. Six patients underwent surgery and radiotherapy. One patient was died during adjuvant chemotherapy. One patient in stage B had local recurrence, one local recurrence and metastases and one had only metastases. In stage C 4 patients was died because of metastases, one had local recurrence and, 3 was died because of other reasons. Patients who was failed, underwent surgery, chemotherapy or radiotherapy, it was dependent of clinical situation. RESULTS: A complete regression was seen in 100% patients in early stages (A and B) and 82% patients in stage C. The 5-year local progression-free survival rate was 91% in early stages and 60% in stage C. The LPFS in whole group was 66.7%. The 5-year disease-free survival rate was 91% in early stages, 46% in stage C. The DSF rate in whole group was 44.4%. The 5-year overall survival rate was 80% in stages A and B, 41.2% in stage C. The OS in whole group was 55.6%. The 5-year survival rate was 20% for patients who had recurrence and/or metastases. CONCLUSION: A combination of surgery and radiotherapy appears to be adequate treatment for early stages (A and B) olfactory neuroblastoma. There are still no clear protocols of treatment patients in stage C.

[SIB-IMRT radiotherapy given concomitantly with cisplatin for locally advanced squamous cell head and neck cancer (SCHNC). Evaluation of the early results and toxicity]. / Zastosowanie techniki SIB-IMRT w leczeniu skojarzonym z jednoczesna chemioterapia u chorych na nowotwory glowy i szyi w III i IVa stopniu zaawansowania. Ocena wczesnych wyników i tolerancji leczenia.

UNLABELLED: Concomitant radiochemotherapy become the treatment of choice for locally advanced SCHNC. This strategy of treatment has a limitation, which is an acute and late toxicity. The IMRT technique provides the possibility of better sparing of healthy tissue. Radiobiological and clinical data also suggest that accelerated fractionation and higher dose per fraction given in GTV may produce better locoregional control. Therefore it might be expected that concomitant chemotherapy and SIB-IMRT radiotherapy could increase locoregional control and reduce acute and late radiation reactions. The evaluation of early results and toxicity of this treatment modality is presented. AIM OF STUDY: The evaluation of the early results and toxicity of SIB-IMRT radiotherapy given concomitantly with cisplatin for locally advanced squamous cell head and neck cancer (SCHNC). METHODS: SIB-IMRT technique was applied. The boost volume was limited to the GTV + 3mm margin (macroscopic tumor extension was defined on the basis of CT and/or MRI examinations). Dose per fraction given to this volume was 2.25 Gy up to 67.5 Gy of total dose. The PTV-CTV + 3mm - was defined as an area of increased risk of microscopic spread. Dose per fraction given to this volume was 2 Gy up to 60 Gy. The PTV1-ETV+ 3mm (electively irradiated volume) received dose per fraction -1.8 Gy up to 54-56 Gy. Overall treatment time was 6 weeks (5 fractions per week, 30 fractions). Concomitant chemotherapy consisted of cisplatin in daily dose100mg/m2 given two times during irradiation (1 and 22 day of treatment). The evaluation of early tolerance was performed once weekly during the treatment than during the follow up every 2 months. The early reactions were scored according to the EORTC/RTOG scale. MATERIAL: Between June 2006 and December 2009 99 patients diagnosed with III and IV clinical stage of SCHNC were treated with this method. 65 patients were diagnosed with oropharyngeal cancer, 18 with laryngeal cancer and 16 with hypopharyngeal cancer. PEG was performed at 65 patients before treatment for better alimentation during radiochemotherapy. RESULTS: No severe life risking complications were observed a no concequentional late effects were observed. Extended mucositis grade III according RTOG/EORTC scale were observed only in boost region in 80% patients just after treatment was completed. In 2 patients ulceration were observed in tumour side which have healed up spontaneously within two months after treatment. 55% patients were suffering for III xerostomia and 41% for middle after the treatment. Majority of side effects were cured within 4 months after irradiation. The PEG was removing in 92% patients 2 months after treatment. The median follow-up time is 28 months (ranged from 14 m to 58 m). Actuarial 2-years overall survival and disease-free survival is respectively 90% and 82%, probability of locoregional recurrence at 2-years is 14% and 5-years estimated is 17,5%. CONCLUSIONS: At the present moment it might be concluded that accelerated radiotherapy with SIB-IMRT given concomitantly with cisplatin produce excellent local control in patients treated of III-IV stage SCHNC without increasing toxicity.

Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND AND PURPOSE: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. MATERIALS AND METHODS: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250mg/day, 500mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2years; secondary endpoints were LDCR at 1year, objective response rate, progression-free survival, overall survival, and safety and tolerability. RESULTS: Gefitinib (250 and 500mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p=0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p=0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. CONCLUSION: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

Quimioterapia basada en platino más cetuximab en el cáncer de cabeza y cuello / Platinum plus cetubimab based quimiotherapy in head and neck cancer

Antecedentes: Cetuximab resulta efectivo en el carcinoma metastático o recurrente de células escamosas de cabeza y cuello, resistente al platino. Se investigó la eficacia de cetuximab más quimioterapia basada en platino como tratamiento de primera línea en pacientes con carcinoma metastático o recurrente de células escamosas de cabeza y cuello. Métodos: Se asignaron al azar 220 pacientes de 442 pacientes elegibles con carcinoma metastático o recurrente de células escamosas de cabeza y cuello sin tratamiento, para recibir cisplatino (a una dosis de 100mg por metro cuadrado de área de superficie corporal el día 1) o carboplatino (en un área por debajo de la curva de 5mg por mililitro por minuto, como infusión intravenosa de 1 hora el día 1) más fluorouracilo (a una dosis de 1000mg por metro cuadrado por día, durante 4 días) cada 3 semanas, por un máximo de 6 ciclos, y 222 pacientes para recibir la misma quimioterapia más cetuximab (a una dosis de 400mg por metro cuadrado en forma inicial, como infusión intravenosa de 2 horas, luego 250mg por metro cuadrado, como infusión intravenosa de 1 hora por semana) durante un máximo de 6 ciclos. Los pacientes con enfermedad estable que recibieron quimioterapia más cetuximab continuaron recibiendo cetuximab hasta la progresión de la enfermedad o hasta la aparición de efectos tóxicos inaceptables, lo que ocurriera primero. Resultados: El agregado de cetuximab a la quimioterapia basada en platino con fluorouracilo (platino-fluorouracilo) prolongó de manera significativa la mediana de la supervivencia global, de 7.4 meses en el grupo de quimioterapia sola a 10.1 meses en el grupo que recibía quimioterapia más cetuximab (índice de riesgo para muerte = 0.80; intervalo de confianza 95%: 0.64-0.99; p = 0.04). El agregado de cetuximab prolongó la mediana del tiempo de supervivencia libre de progresión de 3.3 meses a 5.6 meses (índice de riesgo para la progresión = 0.54; p < 0.001) y aumentó la tasa de respuesta de 20% a 36% (p < 0.001).

Impact of screening kindreds for SDHD p.Cys11X as a common mutation associated with paraganglioma syndrome type 1.

CONTEXT AND OBJECTIVE: Germline mutations of the genes SDHB, SDHC, and SDHD predispose to paraganglioma syndromes. Mutation-specific counseling, risk assessment, and management recommendations ideally should be performed. Here, we provide data for a single common mutation of the SDHD gene. METHODS: The European-American Pheochromocytoma-Paraganglioma Registry served as the source for unrelated index cases affected by pheochromocytoma or paraganglioma. Patients with the SDHD c.33 C-->A (p.Cys11X) germline mutations were reinvestigated by whole-body magnetic resonance imaging and 24-h urinary catecholamine assay. First-degree relatives underwent genetic testing and those testing positive had same clinical investigations. Microsatellite analyses were used to test the hypothesis that all index cases were related and the mutation is a founding one. RESULTS: Sixteen index cases with the mutation SDHD p.Cys11X are registered. After testing their relatives, there were a total of 25 mutation carriers. We excluded seven subjects who inherited the mutation from the mother because of maternal imprinting. Thus, 18 mutation carriers were clinically affected. Among these 16 (89%) had head and neck paragangliomas, six (33%) thoracic tumors, six (33%) extraadrenal retroperitoneal, and five (28%) intraadrenal. Of note, 16 (89%) had multiple tumors at first diagnosis, and one (5%) had signs of malignancy during follow-up. Overall penetrance was 100% at age 54. Haplotype analyses revealed evidence for a founder effect. CONCLUSIONS: The SDHD p.Cys11X mutation is a founding mutation associated with a high penetrance for paraganglial tumors of the skull base, neck, thorax, and retroperitoneum in the first four decades of life and, rarely, with malignancy.

Platinum-based chemotherapy plus cetuximab in head and neck cancer.

BACKGROUND: Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. METHODS: We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first. RESULTS: Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracil) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio for death, 0.80; 95% confidence interval, 0.64 to 0.99; P=0.04). The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) and increased the response rate from 20% to 36% (P<0.001). The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia (19% and 13%, respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group (P=0.02). Of 219 patients receiving cetuximab, 9% had grade 3 skin reactions and 3% had grade 3 or 4 infusion-related reactions. There were no cetuximab-related deaths. CONCLUSIONS: As compared with platinum-based chemotherapy plus fluorouracil alone, cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.)

[Results of treatment in patients with paranasal sinus carcinoma. Analysis of prognostic factors]. / Wyniki leczenia chorych na raka zatok obocznych nosa. Analiza czynników prognostycznych.

Analysis was based on the results of successful and unsuccessful treatment of 137 patients with paranasal sinus cancer at the Oncology Centre in Warsaw between 1987-2002. Patients with clinical stages T3 and T4 constituted 87% of cases (110 patients). Radical treatment was performed on 84 patients. Five-year overall survival in 137 cases amounted to 27%; and survival without recurrence was 24%. Five-year overall and recurrence-free survial among patients treated with surgery and radiotherapy were 36% and 32% retrospectively. Multivariate analysis of 61 patients with complete data, who were treated with radical surgery and radiotherapy, emphasized the influence of prognostic factors on survival. A worse prognosis correlated with advanced locoregional T and N stage. It is evident that total dose greater than 6000 cGy had a clear impact on the results of treatment. It was also shown that planning with the manually and hand-measured isodoses impacted negatively on the survival in comparison with 2D and 3D planning. Analysis of recurrence-free survival showed that metastatis to the lymph nodes, and a manually-planned treatment method, had a negative impact on the results of treatment. It is asserted that local recurrences are the main cause of failure in cases treated with surgery and radiotherapy.