Hypofractionated Post-Prostatectomy Radiotherapy in 16 Fractions: A Single-Institution Outcome.

BACKGROUND: The optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with intensity-modulated radiotherapy. The treatment schedule selection was motivated by limited technology resources and was radiobiologically dose-escalated. METHODS: One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early-salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed planning target volume was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v. 4 for Adverse Events scale was used for toxicity grading. RESULTS: The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival (DMFS) was 95.7% and overall survival was 98.8%. Treatment indication (ART or eSRT vs. SRT) was the only significant factor for bRFS (HR 0.15, 95% CI 0.05-0.47, p = 0.001) and DMFS (HR 0.16, 95% CI 0.03-0.90; p = 0.038). Acute gastrointestinal (GI) toxicity grade 2 was recorded in 24%, grade 3 in 2%, acute genitourinary (GU) toxicity grade 2 in 10% of patients, and no grade 3. A cumulative rate of late GI toxicity grade ≥ 2 was observed in 9% and late GU toxicity grade ≥ 2 in 16% of patients. CONCLUSIONS: The observed results confirmed efficacy and showed a higher than anticipated rate of early GI, late GI, and GU toxicity of post-prostatectomy radiobiologically dose-escalated hypofractionated radiotherapy in 16 daily fractions.

Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives.

Over the last two decades, human papillomavirus (HPV) has caused a new pandemic of cancer in many urban areas across the world. The new entity, HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), has been at the center of scientific attention ever since, not only due to its distinct biological behavior, but also because of its significantly better prognosis than observed in its HPV-negative counterpart. The very good treatment outcomes of the disease after primary therapy (minimally-invasive surgery, radiation therapy with or without chemotherapy) resulted in the creation of a separate staging system, reflecting this excellent prognosis. A substantial proportion of newly diagnosed HPV-driven OPSCC is diagnosed in stage I or II, where long-term survival is observed worldwide. Deintensification of the primary therapeutic methods, aiming at a reduction of long-term toxicity in survivors, has emerged, and the quality of life of the patient after treatment has become a key-point in many clinical trials. Current treatment recommendations for the treatment of HPV-driven OPSCC do not differ significantly from HPV-negative OPSCC; however, the results of randomized trials are eagerly awaited and deemed necessary, in order to include deintensification into standard clinical practice.

Radical external beam re-irradiation in the treatment of recurrent head and neck cancer: Critical review.

Management of patients with recurrent head and neck cancer remains a challenge for the surgeon as well as the treating radiation oncologist. Even in the era of modern radiotherapy, the rate of severe toxicity remains high with unsatisfactory treatment results. Intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and heavy-ion irradiation have all emerged as highly conformal and precise techniques that offer many radiobiological advantages in various clinical situations. Although re-irradiation is now widespread in clinical practice, little is known about the differences in treatment response and toxicity using diverse re-irradiation techniques. In this review, we provide a comprehensive overview of the role of radiation therapy in recurrent or second primary head and neck cancer including patient selection, therapeutic outcome, and risk using different re-irradiation techniques. Critical review of published evidence on IMRT, SBRT, and heavy-ion full-dose re-irradiation is presented including data on locoregional control, overall survival, and toxicity.

Recurrent Nasopharyngeal Cancer: Critical Review of Local Treatment Options Including Recommendations during the COVID-19 Pandemic.

Recurrent nasopharyngeal carcinoma represents an extremely challenging therapeutic situation. Given the vulnerability of the already pretreated neurological structures surrounding the nasopharynx, any potential salvage retreatment option bears a significant risk of severe complications that result in high treatment-related morbidity, quality of life deterioration, and even mortality. Yet, with careful patient selection, long-term survival may be achieved after local retreatment in a subgroup of patients with local or regional relapse of nasopharyngeal cancer. Early detection of the recurrence represents the key to therapeutic success, and in the case of early stage disease, several curative treatment options can be offered to the patient, albeit with minimal support in prospective clinical data. In this article, an up-to-date review of published evidence on modern surgical and radiation therapy treatment options is summarized, including currently recommended treatment modifications of both therapeutic approaches during the coronavirus disease 2019 pandemic.

Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer.

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 "prospective" studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors-resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)-showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.

Small Subset of Adenoid Cystic Carcinoma of the Skin Is Associated With Alterations of the MYBL1 Gene Similar to Their Extracutaneous Counterparts.

Adenoid cystic carcinoma (ACC) of the skin is a rare malignant neoplasm histologically identical to homonymous tumors in other organs. Cutaneous ACC has been found to harbor MYB gene activations, either through MYB chromosomal abnormalities or by generation of the MYB-NFIB fusion. In salivary gland ACC, in addition to the MYB gene, alterations in MYBL1, the gene closely related to MYB, have been reported. We studied 10 cases of cutaneous ACC (6 women, 4 men; and age range 51-83 years) for alterations in the MYB, NFIB, and MYBL1 genes, using FISH and PCR. MYB break-apart and NFIB break-apart tests were positive in 4 and 5 cases, respectively. MYB-NFIB fusions were found in 4 cases. The break of MYBL1 was found in 2 cases, and in one of them, the NFIB break-apart probe was positive, strongly indicating a MYBL1-NFIB fusion. In 2 cases, the MYB break-apart test was positive, whereas no MYB-NFIB was detected, strongly suggesting another fusion partner. It is concluded that MYBL1 alterations are detected in primary cutaneous ACC but are apparently less common compared with MYB and NFIB alterations.

Radiation Therapy in Extensive Stage Small Cell Lung Cancer.

Lung cancer is the major cancer killer in the Western world, with the small cell lung cancer (SCLC) representing around 15-20% of all lung cancers. Extensive disease small cell lung cancer (ED SCLC) is found in approximately two-thirds of all cases, composed of both metastatic (M1) and non-metastatic (but presumably with tumor burden too large for locoregional-only approach) variant. Standard treatment options involve chemotherapy (CHT) over the past several decades. Radiation therapy (RT) had mostly been used in palliation of locoregional and/or metastatic disease. In contrast to its established role in treating metastatic disease, thoracic RT (TRT) had never been established as important part of the treatment aspects in this setting. In the past two decades, thoracic oncologists have witnessed wide introduction of modern RT and CHT aspects in ED SCLC, which led to more frequent use of RT and rise in the number of clinical studies. Since the pivotal study of Jeremic et al., who were the first to show importance of TRT in ED SCLC, a number of single-institutional studies have reconfirmed this observation, while recent prospective randomized trials (CREST and RTOG 0937) brought more substance to this issue. Similarly, the issue of prophylactic cranial irradiation was investigated in EORTC and the Japanese study, respectively, bringing somewhat conflicting results and calling for additional research in this setting. Future studies in ED SCLC could incorporate questions of RT dose and fractionation as well as the number of CHT cycles and type of combined Rt-CHT (sequential vs concurrent).

Combined modality therapy in Stage IIIA non-small cell lung cancer: clarity or confusion despite the highest level of evidence?

Recent years have witnessed a number of clinical trials in Stage IIIA non-small cell lung cancer (NSCLC) comparing (A) induction chemotherapy (CHT) with induction CHT and radiotherapy (RT), each followed by surgery; (B) either induction CHT or induction RT-CHT, each followed by surgery, with definitive RT-CHT (no surgery). Due to the heterogeneity of patient, tumor and treatment characteristics across these trials, various meta-analyses (MAs) have been performed to define the optimal treatment approach in this setting for this clinical presentation. Six such MAs exist. In spite of the differences between MAs, it appears that RT does not add extra benefit to induction CHT administered before surgery, and that a trimodality (i.e. including surgery) regimen is not superior to definitive concurrent RT-CHT. While one can consider both induction CHT followed by surgery and exclusive concurrent RT-CHT as feasible in this setting, lack of pre-treatment predictive factors identifying patients who might preferentially benefit from a surgical approach limits its use to well-planned clinical trials.

Warthin-like papillary renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 11 cases.

Oncocytic papillary renal cell carcinoma (PRCC) is a distinct subtype of PRCC, listed as a possible new variant of PRCC in the 2016 WHO classification. It is composed of papillae aligned by large single-layered eosinophilic cells showing linearly arranged oncocytoma-like nuclei. We analyzed clinicopathologic, morphologic, immunohistochemical and molecular-genetic characteristics of 11 oncocytic PRCCs with prominent tumor lymphocytic infiltrate, morphologically resembling Warthin's tumor. The patients were predominantly males (8/11, 73%), with an average age of 59years (range 14-76), and a mean tumor size of 7cm (range 1-22cm). Tumors had the features of oncocytic PRCCs with focal pseudostratification in 8/11 cases and showed dense stromal inflammatory infiltration in all cases. Papillary growth pattern was predominant, comprising more than 60% of tumor volume. Tubular and solid components were present in 5 and 3 cases, respectively. Uniform immunohistochemical positivity was found for AMACR, PAX-8, MIA, vimentin, and OSCAR. Tumors were mostly negative for carboanhydrase 9, CD117, CK20, and TTF-1. Immunohistochemical stains for DNA mismatch repair proteins MLH1 and PMS2 were retained in all cases, while MSH2 and MSH6 were negative in 1 case. Tumor infiltrating lymphocytes (TILs) consisted of both B and T cells. Chromosomal copy number variation analysis showed great variability in 5 cases, ranging from a loss of one single chromosome to complex genome rearrangements. Only one case showed gains of chromosomes 7 and 17, among other aberrations. In 4 cases no numerical imbalance was found. Follow up data was available for 9 patients (median 47.6months, range 1-132). In 6 patients no lethal progression was noted, while 3 died of disease. In conclusion, Warthin-like PRCC is morphologically very close to oncocytic PRCC, from which it differs by the presence of dense lymphoid stroma. Chromosomal numerical aberration pattern of these tumors is variable; only one case showed gains of chromosomes 7 and 17. Warthin-like PRCC is a potentially aggressive tumor since a lethal outcome was recorded in 3/9 cases.

Endometrial Endometrioid Carcinoma With Large Cystic Growth Configuration and Deceptive Pattern of Invasion Associated With Abundant Nodular Fasciitis-like Stroma: A Unique Hitherto Unreported Histology in Endometrioid Carcinoma.

We describe a case of an unusual endometrial endometrioid carcinoma occurring in a 67-year-old woman. The tumor involved uterine corpus as well as lower uterine segment and presented as polypoid tumor protruding through the cervical orifice. Microscopically, the tumor was characterized by broad zones of cytologically bland fibromyxoid stroma resembling nodular fasciitis, showing vaguely nodular architecture. Neoplastic glands were characterized by interconnected elongated slit-like and large cystic profiles, mostly lined by flattened epithelium with variable squamous differentiation, whereas typical columnar endometrioid cells were only focally present. Voluminous nodules of the stroma produced phyllodes-like appearance of the tumor. The tumor showed some resemblance to the microcystic, elongated, and fragmented (MELF) glands growth pattern, but in contrast with MELF pattern, where fibromyxoid change occurs focally, in the presented case abundant myofibroblastic proliferation was present throughout the tumor and the neoplastic glands showed anastomosing "large cystic" rather than "small cystic" profiles. Some of the neoplastic glands presented almost complete or complete squamous differentiation, with relatively bland-looking squamous cells and no hint of endometrioid differentiation, which resulted in initial misdiagnosis of Müllerian adenofibroma. We believe that nodular fasciitis-like pattern represents yet undescribed, and diagnostically challenging pattern of invasion in endometrial endometrioid carcinoma.

Human Trichinella infection outbreaks in Slovakia, 1980-2008.

Trichinellosis, a parasitic zoonosis with world-wide distribution, causes serious health problems in humans and is also of economic importance. In Slovakia the most frequent species is T. britovi, causing disease mainly in wild life species. T. spiralis occurs less frequently and T. pseudospiralis only sporadically. The paper describes the epidemiology of six human Trichinella infection outbreaks recorded in Slovakia between 1980 and 2008. Before 1990 wild boar meat was the main source of infection. Later, risk farm practices, especially feeding of pigs with the wild animal´s offal contributed to the formation of synanthropic cycle and pig meat caused the epidemics in 1990, 2001 and 2008. Sausages prepared from pork and T. britovi infected dog meat and offered as a local food specialty on traditional folk festival in 1998 (Brezno district, Central Slovakia) were the source of the largest human outbreak recorded in Slovakia. The anti-Trichinella antibodies were detected in 336 event visitors. The main reason of repeated human epidemics in Slovakia has been the permanent circulation of Trichinella spp. in sylvatic cycle, especially in red foxes and wild boars. High population density of both animal species, persistent prevalence of trichinellosis in wild boars and even increasing positivity of red foxes suggest that the risk of human outbreaks in Slovakia persists.

Origin of cystic squamous cell carcinoma metastases in head and neck lymph nodes: Addition of EBV testing improves diagnostic accuracy.

Most cases of cystic squamous cell carcinoma (SCC) metastases in the upper neck are associated with an oropharyngeal primary, namely human papillomavirus (HPV)-associated SCC arising in the palatine or lingual tonsil. A retrospective study was performed on 22 patients who presented with cystic head and neck SCC metastases. The purpose of the study was to find out whether histological characteristics, p16 protein expression, HPV and Epstein-Barr virus (EBV) status could be useful in predicting the localization of the primary tumor. The primary site was identified in 20 of 22 patients and included the oropharynx in 14 patients (63.6%), the nasopharynx in 3 patients (13.6%), the lungs in 2 cases (9%), and the skin of the auricle in one case (4.5%). No primary was found in two patients (9%). Sixteen of 17 cases (94.1%) originating in Waldayer's ring (oropharynx and nasopharynx), and both cases with an unknown primary showed morphology of non-keratinizing SCC or non-keratinizing SCC with maturation. All tumors with oropharyngeal primary and both cases with unknown primary showed diffuse p16 staining and presence of HPV DNA. All three cystic metastases of nasopharyngeal carcinoma were EBV-positive and p16/HPV-negative. In contrast, cutaneous and pulmonary metastases showed morphology of a well differentiated keratinizing SCC and poorly differentiated keratinizing SCC, respectively, and were HPV/EBV-negative. We confirmed that cystic SCC lymph node metastases of the head and neck region are strongly associated with the occult primary localized in the oropharynx. The oropharyngeal origin should always be corroborated by p16 immunohistochemistry and HPV-specific testing because SCC arising in other sites, such as nasopharynx, skin or lungs may manifest with cystic neck metastases as well. Addition of EBV testing in p16/HPV-negative cases can disclose the nasopharyngeal origin of the cystic neck metastases in a subset of cases.

Surgery for Stage IIIA Non-Small-cell Lung Cancer: Lack of Predictive and Prognostic Factors Identifying Any Subgroup of Patients Benefiting From It.

Although a trimodality regimen for patients with stage IIIA/pN2 non-small-cell lung cancer (NSCLC) has been variably used owing to limited evidence for its benefits, it remains unknown whether any patient subgroup actually receives benefit from such an approach. To explore this question, the published data were reviewed from 1990 to 2015 to identify the possible predictors and prognosticators in this setting. Overall survival was the endpoint of our study. Of 27 identified studies, none had studied the predictors of improved outcomes with trimodality treatment. Of the potential patient- and tumor-related prognosticators, age, gender, and histologic type were the most frequently formally explored. However, none of the 3 was found to influence overall survival. The most prominent finding of the present review was the substantial lack of data supporting a trimodality treatment approach in any patient subgroup. As demonstrated in completed prospective randomized studies, the use of surgery for stage IIIA NSCLC should be limited to well-defined clinical trials.

Postoperative Adjuvant Lapatinib and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib Monotherapy in High-Risk Patients With Resected Squamous Cell Carcinoma of the Head and Neck: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study.

PURPOSE: This multicenter phase III study evaluated the efficacy and safety of lapatinib, an epidermal growth factor receptor/ErbB2 inhibitor, administered concomitantly with chemoradiotherapy and as maintenance monotherapy in patients with high-risk surgically treated squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with resected stage II to IVA SCCHN, with a surgical margin ≤ 5 mm and/or extracapsular extension, were randomly assigned to chemoradiotherapy (66 Gy total radiation dose and cisplatin 100 mg/m(2) per day administered on days 1, 22, and 43) plus placebo or lapatinib (1,500 mg per day) before and during chemoradiotherapy, followed by 12 months of maintenance monotherapy. RESULTS: Six hundred eighty-eight patients were enrolled (lapatinib, n = 346; placebo, n = 342). With a median follow-up time of 35.3 months, the study ended early because of the apparent plateauing of disease-free survival (DFS) events. Median DFS assessed by an independent review committee was 53.6 months and not reached for lapatinib and placebo, respectively (hazard ratio, 1.10; 95% CI, 0.85 to 1.43). Investigator-assessed results confirmed the independent review committee assessment. No significant differences in DFS by human papillomavirus status or overall survival were observed between treatment arms. Similar numbers of patients in both treatment arms experienced adverse events (AEs), with more patients in the lapatinib arm than the placebo arm experiencing serious AEs (48% v 40%, respectively). The most commonly observed treatment-related AEs were diarrhea and rash, both predominantly in the lapatinib arm. CONCLUSION: Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk SCCHN.

Guidelines for equipment and staffing of radiotherapy facilities in the European countries: final results of the ESTRO-HERO survey.

BACKGROUND AND PURPOSE: In planning to meet evidence based needs for radiotherapy, guidelines for the provision of capital and human resources are central if access, quality and safety are not to be compromised. A component of the ESTRO-HERO (Health Economics in Radiation Oncology) project is to document the current availability and content of guidelines for radiotherapy in Europe. MATERIALS AND METHODS: An 84 part questionnaire was distributed to the European countries through their national scientific and professional radiotherapy societies with 30 items relating to the availability of guidelines for equipment and staffing and selected operational issues. Twenty-nine countries provided full or partial evaluable responses. RESULTS: The availability of guidelines across Europe is far from uniform. The metrics used for capital and human resources are variable. There seem to have been no major changes in the availability or specifics of guidelines over the ten-year period since the QUARTS study with the exception of the recent expansion of RTT staffing models. Where comparison is possible it appears that staffing for radiation oncologists, medical physicists and particularly RTTs tend to exceed guidelines suggesting developments in clinical radiotherapy are moving faster than guideline updating. CONCLUSION: The efficient provision of safe, high quality radiotherapy services would benefit from the availability of well-structured guidelines for capital and human resources, based on agreed upon metrics, which could be linked to detailed estimates of need.

Canine dirofilariosis under specific environmental conditions of the Eastern Slovak Lowland.

The aim of the present study was to collect data from Eastern Slovak Lowland, southern Slovakia, to assess risk of the spread of canine dirofilariosis. Climate and environmental conditions in the Eastern Slovak Lowland are ideally suitable for the occurrence of vector-borne diseases. In the past, an endemic locality of dangerous mosquito transmitted malaria was found in this area. Today, another zoonotic parasitic disease threatens--dirofilariosis. The results of the first detailed study revealed a 34.44% prevalence in dogs harbouring dirofilariae. D. repens was diagnosed in all infected specimen, with 2 individuals being co-infected also with D. immitis.