The impact of COVID-19 on oncology professionals—one year on: lessons learned from the ESMO Resilience Task Force survey series

COVID-19; Oncology professionals; ResilienceCOVID-19; Profesionales de la oncología; ResilienciaCOVID-19; Professionals de l'oncologia; ResiliènciaBackground COVID-19 has had a significant impact on the well-being and job performance of oncology professionals globally. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration set out to investigate and monitor well-being since COVID-19 in relation to work, lifestyle and support factors in oncology professionals 1 year on since the start of the pandemic. Methods An online, anonymous survey was conducted in February/March 2021 (Survey III). Key outcome variables included risk of poor well-being or distress (expanded Well-Being Index), feeling burnout (single item from expanded Well-Being Index), and job performance since COVID-19. Longitudinal analysis of responses to the series of three surveys since COVID-19 was carried out, and responses to job demands and resources questions were interrogated. SPSS V.26.0/V.27.0 and GraphPad Prism V9.0 were used for statistical analyses. Results Responses from 1269 participants from 104 countries were analysed in Survey III: 55% (n = 699/1269) female, 54% (n = 686/1269) >40 years, and 69% (n = 852/1230) of white ethnicity. There continues to be an increased risk of poor well-being or distress (n = 464/1169, 40%) and feeling burnout (n = 660/1169, 57%) compared with Survey I (25% and 38% respectively, P < 0.0001), despite improved job performance. Compared with the initial period of the pandemic, more participants report feeling overwhelmed with workload (45% versus 29%, P < 0.0001). There remain concerns about the negative impact of the pandemic on career development/training (43%), job security (37%). and international fellowship opportunities (76%). Alarmingly, 25% (n = 266/1086) are considering changing their future career with 38% (n = 100/266) contemplating leaving the profession. Conclusion Oncology professionals continue to face increased job demands. There is now significant concern regarding potential attrition in the oncology workforce. National and international stakeholders must act immediately and work closely with oncology professionals to draw up future-proof recovery plans.This work was supported by the European Society for Medical Oncology (ESMO): for license to use Qualtrics (online survey platform), and publication of figure fee

Radical Hemiscrotectomy and En Bloc Orchidectomy: Surgical Technique and Perioperative and Oncologic Outcomes of a Supra-Regional UK Referral Centre

Background and purpose: Hemiscrotectomy with en bloc orchidectomy represents a radical primary, completion, or salvage option in men with inguinoscrotal cancers. We describe our surgical technique and peri-operative and oncological outcomes. Patients and methods: Retrospective cohort study of 16 men treated at a supra-regional referral centre with open radical hemiscrotectomy with or without en bloc orchidectomy between 2010 and 2020. Peri-operative and survival outcomes were analysed. Results: Radical hemiscrotectomy with or without en bloc orchidectomy was performed on 16 patients comprising 7 well-differentiated liposarcomas, 4 dedifferentiated liposarcomas, 2 leiomyosarcomas, 1 mesothelioma, 1 rhabdomyosarcoma and 1 mammary type myofibroblastoma. Primary hemiscrotectomy was performed in four, completion hemiscrotectomy in nine and salvage hemiscrotectomy in three. The median hospital stay was 2 days [interquartile range (IQR) 2-4]. Four patients (25%) had post-operative complications including wound infection or haematoma. During a median follow-up of 18 months (IQR 2-66), one patient (6%) died following a recurrence in the pelvis and retroperitoneum. Discussion: and Conclusions If careful dissection is performed, radical hemiscrotectomy and en bloc orchidectomy is a radical but safe procedure with a short hospital stay. Haematoma and infection represent the main complications, and within limited follow-up most men showed no recurrence

First-line salvage treatment options for germ cell tumor patients failing stage-adapted primary treatment : A comprehensive review compiled by the German Testicular Cancer Study Group

Purpose In this review, we summarize and discuss contemporary treatment standards and possible selection criteria for decision making after failure of adjuvant or first-line cisplatin-based chemotherapy for primarily localized or metastatic germ cell tumors. Methods This work is based on a systematic literature search conducted for the elaboration of the first German clinical practice guideline to identify prospective clinical trials and retrospective comparative studies published between Jan 2010 and Feb 2021. Study end points of interest were progression-free (PFS) and overall survival (OS), relapse rate (RR), and/or safety. Results Relapses of clinical stage I (CS I) patients irrespective of prior adjuvant treatment after orchiectomy are treated stage adapted in accordance for primary metastatic patients. Surgical approaches for sole retroperitoneal relapses are investigated in ongoing clinical trials. The appropriate salvage chemotherapy for metastatic patients progressing or relapsing after first-line cisplatin-based chemotherapy is still a matter of controversy. Conventional cisplatin-based chemotherapy is the international guideline-endorsed standard of care, but based on retrospective data high-dose chemotherapy and subsequent autologous stem cell transplantation may offer a 10–15% survival benefit for all patients. Secondary complete surgical resection of all visible residual masses irrespective of size is paramount for treatment success. Conclusions Patients relapsing after definite treatment of locoregional disease are to be treated by stage-adapted first-line standard therapy for metastatic disease. Patients with primary advanced/metastatic disease failing one line of cisplatin-based combination chemotherapy should be referred to GCT expert centers. Dose intensity is a matter of ongoing debate, but sequential high-dose chemotherapy seems to improve patients’ survival

Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry

Purpose Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions < 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography (PET)-negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking. Patients and Methods We retrospectively identified 90 patients with metastatic seminoma with PET-positive residual lesions after chemotherapy. Patients with elevated α-fetoprotein or nonseminomatous histology were excluded. We analyzed the post-PET management and its impact on relapse and survival and calculated the positive predictive value (PPV) for PET. Results Median follow-up time was 29 months (interquartile range [IQR], 10 to 62 months). Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm), with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was 6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients (10%) and radiotherapy in four patients (4%). Histology of the resected specimen was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11 (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after resection, and in two (22%) of nine patients after biopsy. All but one patient who experienced relapse were successfully treated with salvage therapy. The PPV for FDG-PET was 23%. Conclusion FDG-PET has a low PPV for vital tumor in residual lesions after chemotherapy in patients with metastatic seminoma. This cautions against clinical decisions based on PET positivity alone

Therapy of clinical stage IIA and IIB seminoma: a systematic review

Purpose The optimal treatment for clinical stage (CS) IIA/IIB seminomas is still controversial. We evaluated current treatment options. Methods A systematic review was performed. Only randomized clinical trials and comparative studies published from January 2010 until February 2021 were included. Search items included: seminoma, CS IIA, CS IIB and therapy. Outcome parameters were relapse rate (RR), relapse-free (RFS), overall and cancer-specific survival (OS, CSS). Additionally, acute and long-term side effects including secondary malignancies (SMs) were analyzed. Results Seven comparative studies (one prospective and six retrospective) were identified with a total of 5049 patients (CS IIA: 2840, CS IIB: 2209). The applied treatment modalities were radiotherapy (RT) (n = 3049; CS IIA: 1888, CSIIB: 1006, unknown: 155) and chemotherapy (CT) or no RT (n = 2000; CS IIA: 797, CS IIB: 1074, unknown: 129). In CS IIA, RRs ranged from 0% to 4.8% for RT and 0% for CT. Concerning CS IIB RRs of 9.5%–21.1% for RT and of 0%–14.2% for CT have been reported. 5-year OS ranged from 90 to 100%. Only two studies reported on treatment-related toxicities. Conclusions RT and CT are the most commonly applied treatments in CS IIA/B seminoma. In CS IIA seminomas, RRs after RT and CT are similar. However, in CS IIB, CT seems to be more effective. Survival rates of CS IIA/B seminomas are excellent. Consequently, long-term toxicities and SMs are important survivorship issues. Alternative treatment approaches, e.g., retroperitoneal lymph node dissection (RPLND) or dose-reduced sequential CT/RT are currently under prospective investigation

Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy.

PURPOSE Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. METHODS AND MATERIALS Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. RESULTS With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. CONCLUSIONS Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy

The concerns of oncology professionals during the COVID-19 pandemic results from the ESMO Resilience Task Force survey II

Background The COVID-19 pandemic has resulted in significant changes to professional and personal lives of oncology professionals globally. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration aimed to provide contemporaneous reports on the impact of COVID-19 on the lived experiences and well-being in oncology. Methods This online anonymous survey (July-August 2020) is the second of a series of global surveys launched during the course of the pandemic. Longitudinal key outcome measures including well-being/distress (expanded Well-being Index—9 items), burnout (1 item from expanded Well-being Index), and job performance since COVID-19 were tracked. Results A total of 942 participants from 99 countries were included for final analysis: 58% (n = 544) from Europe, 52% (n = 485) female, 43% (n = 409) ≤40 years old, and 36% (n = 343) of non-white ethnicity. In July/August 2020, 60% (n = 525) continued to report a change in professional duties compared with the pre-COVID-19 era. The proportion of participants at risk of poor well-being (33%, n = 310) and who reported feeling burnout (49%, n = 460) had increased significantly compared with April/May 2020 (25% and 38%, respectively; P < 0.001), despite improved job performance since COVID-19 (34% versus 51%; P < 0.001). Of those who had been tested for COVID-19, 8% (n = 39/484) tested positive; 18% (n = 7/39) felt they had not been given adequate time to recover before return to work. Since the pandemic, 39% (n = 353/908) had expressed concerns that COVID-19 would have a negative impact on their career development or training and 40% (n = 366/917) felt that their job security had been compromised. More than two-thirds (n = 608/879) revealed that COVID-19 has changed their outlook on their work-personal life balance. Conclusion The COVID-19 pandemic continues to impact the well-being of oncology professionals globally, with significantly more in distress and feeling burnout compared with the first wave. Collective efforts from both national and international communities addressing support and coping strategies will be crucial as we recover from the COVID-19 crisis. In particular, an action plan should also be devised to tackle concerns raised regarding the negative impact of COVID-19 on career development, training, and job security

Second-Generation Antiandrogen Therapy Radiosensitizes Prostate Cancer Regardless of Castration State through Inhibition of DNA Double Strand Break Repair

(1) Background: The combination of the first-generation antiandrogens and radiotherapy (RT) has been studied extensively in the clinical setting of prostate cancer (PCa). Here, we evaluated the potential radiosensitizing effect of the second-generation antiandrogens abiraterone acetate, apalutamide and enzalutamide. (2) Methods: Cell proliferation and agarose-colony forming assay were used to measure the effect on survival. Double strand break repair efficiency was monitored using immunofluorescence staining of &gamma;H2AX/53BP1. (3) Results: We report retrospectively a minor benefit for PCa patients received first-generation androgen blockers and RT compared to patients treated with RT alone. Combining either of the second-generation antiandrogens and 2Gy suppressed cell growth and increased doubling time significantly more than 2Gy alone, in both hormone-responsive LNCaP and castration-resistant C4-2B cells. These findings were recapitulated in resistant sub-clones to (i) hormone ablation (LNCaP-abl), (ii) abiraterone acetate (LNCaP-abi), (iii) apalutamide (LNCaP-ARN509), (iv) enzalutamide (C4-2B-ENZA), and in castration-resistant 22-RV1 cells. This radiosensitization effect was not observable using the first-generation antiandrogen bicalutamide. Inhibition of DNA DSB repair was found to contribute to the radiosensitization effect of second-generation antiandrogens, as demonstrated by a significant increase in residual &gamma;H2AX and 53BP1 foci numbers at 24h post-IR. DSB repair inhibition was further demonstrated in 22 patient-derived tumor slice cultures treated with abiraterone acetate before ex-vivo irradiation with 2Gy. (4) Conclusion: Together, these data show that second-generation antiandrogens can enhance radiosensitivity in PCa through DSB repair inhibition, regardless of their hormonal status. Translated into clinical practice, our results may help to find additional strategies to improve the effectiveness of RT in localized PCa, paving the way for a clinical trial

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic:A Survey of International Expertise Centers

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity

Zur Rolle der aberranten DNA-Hypermethylierung des Tumorsuppressorgens Inter-alpha-Trypsin-Inhibitor heavy chain 5 (ITIH5) bei akuter myeloischer Leukämie

Acute myeloid leukemia (AML) is a clonal disorder resulting from uncontrolled proliferation of hematopoietic stem cells. Important genetic findings in AML comprise chromosomal translocations involving different transcription factors and activating point mutations in multiple signal transduction pathways. Hypermethylation of CpG islands within gene promoter regions in collaboration with deacetylation and other histone modifications is associated with transcriptional inactivation and represents, in addition to genetic aberrations, an important mechanism of gene silencing in human cancers. Inter-α-trypsin inhibitors are serum proteases consisting of one light chain, bikunin, and two homologous heavy chains (ITIHs), which stabilize the extracellular matrix (ECM). The putative tumor suppressor gene ITIH5 is the most recent member of the ITIH family and has been reported to be downregulated by DNA hypermethylation in breast cancer. In this study, we determined the methylation status of the promoter-associated CpG island of ITIH5 in both AML cell lines and primary AML patient samples. Methylation specific polymerase chain reaction analysis revealed that the ITIH5 promoter region was hypermethylated in the AML cell lines HL60 and KG-1a. Treatment of cell lines that carry a hypermethylated ITIH5 gene with the demethylating agent 5-aza-2’-deoxycytidine resulted in partial promoter demethylation. We then analyzed the ITIH5 methylation status in primary mononuclear cells obtained from 104 patients with newly diagnosed AML. The frequency of aberrant methylation among the primary patient samples was 14.4% (15 of 104). Among clinical prognostic parameters, we found no significant correlation between hypermethylation of ITIH5 and cytogenetics, elevated serum levels of lactate dehydrogenase, French–American–British subtype, gender, age, peripheral blood cell counts, and overall survival (p=0.08). Since there was a trend toward an association between increased WBC and ITIH5 promoter hypermethylation (p=0.24), we hypothesize that epigenetic dysregulation of ITIH5 may result in an impaired interaction between the leukemic clone and its’ surrounding ECM in the bone marrow. Additionally, the OS curve implies a slight, but not statistically significant advantage for patients who carry a hypermethylated ITIH5 promoter. Concluding, ITIH5 promoter hypermethylation is a novel epigenetic event in AML that may contribute to leukemogenesis by interfering with the interaction between the ECM and the leukemic clone. Though ITIH5 promoter hypermethylation does not appear to be an independent prognostic factor in AML, as it was recently demonstrated in breast cancer