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Academic work, research and major achievements by Prof. Dr. med. Hans-Joachim Schmoll from 1970 through 2016

1. Overview

Since many years, Prof. Schmoll is the most recognized, accepted and influential german medical oncologist- but not only in Germany, but also in Europe as well as in the US, South-America and Asia. This is based on the huge amount of clinically highly important scientific research with major relevance for defining new treatment standards, particularly in the field of GU- and GI-cancer, as well as his tremendous activity to develop and support oncologic education, building up of research structures, in particular in germany , and involvement in national and international organization like AIO, ESMO, ASCO, SLAGO and many more other national oncology societies and organisations. With currently 420 scientific publications (pubmed), several of them belonging to the highest cited papers of some of the journals, a very high cumulative impact factor of 1807, an extremely high citation rate between 1150 and 1380 citations per year in the last 3 years, and a Citation Factor (Hirsch) as high as 64 (!), Prof. Schmoll had and has a very strong scientific impact and influence for the field of medical oncology worldwide.

 

Prof. Schmoll has contributed continuously key research to the field of clinical oncology for germ cell cancer and gastrointestinal cancer, in particular colon- and rectal cancer, and several other solid tumor sites. He has set up the first international consensus group and guideline for germ cell cancer (EGCCCG and ESMO, 2008), as well as for the all stages of colon- and rectal cancer (ESMO guideline 2012)-both guidelines had set the standard for the clinical management in most countries.

 

In Germany, Prof. Schmoll had set up over the last decades the structures for cooperative clinical and translational research in medical as well as multidisciplinary oncology, by building up the cooperative clinical trials in all fields of oncology, as well as the corresponding network and structures within the AIO. By this mean, he also was instrumental for the scientific and carrier development of the younger generation of medical oncologists and the fellows; most of his former fellows have achieved a high level of national and international recognition, and are translating the effort of Prof. Schmoll into further improvement. 

 

Prof. Schmoll had a longtime active part in the ESMO, where he was long term member of the executive board and founding chair of the “Multidisciplinary Oncology Committee” (MOC). He served as the scientific chair of the Istanbul ESMO-congress, where he introduced the track system for an innovative structure of the scientific committee. Furthermore, by changing the rules for board positions in the AIO which required the ESMO-Examination as prerequisite, he strongly increased the number of ESMO members coming from Germany-a group which represents now largest proportion of national members within the ESMO.

 

Finally, Prof. Schmoll was key instrumental for the recognition of “Med-Onc” in the parliament, since he had successfully set up an alliance between the german society for HemOnc, the German Chamber of Medicine (Ärztekammer), the parliament and the german  EU-representatives, in order to achieve the mostly relevant number of votings.

 

In ASCO, Prof. Schmoll served numerous times as member of the scientific committee, faculty, and invited speaker.

 

 The most important earnings of Prof. Schmoll, besides his research achievements, and the development of clinical research and supporting structures for  medical oncology and oncologists in germany, is his tremendous impact on the education and development of management quality in german speaking countries over the last 30 years. Besides more than 12  books and monographs, he had written and edited the reference book for medical and interdisciplinary oncology (600 pages, 3 volumes, 5th edition in preparation, each edition 10.000 books, plus electronic edition), which serves since the first edition as the standard reference  book for everybody treating cancer in those countries. Indeed, this book serves continuously as the source for education in all fields of medical and interdisciplinary oncology as well as supportive care.


2. Scientific work

 

2.1. Development of clinical research structures and researches in the AIO

All of the trials have been done in the framework of the AIO- Germ Cell- and the Colorectal Cancer trial groups, which Prof. Schmoll has built up and developed as founding chair to one of the most important  and successful clinical trial groups for CRC and upper GI-cancer and Germ cell tumor in Europe and worldwide. In summary, in this large field of gastro-intestinal cancer, in particular colon – and rectal cancer, as well as germ cell cancer, Prof. Schmoll and his group have added major contributions to the development of modern standard treatment strategies; through this cooperative academic work, he was also instrumental for the development of a cooperative, multimodal treatment and research approach in Germany including surgeons, urologists, radiotherapists, interventionalists and medical oncologists for  clinical research as well as daily multidisciplinary treatment decisions and performance.

 

 

2.2. Clinical scientific research and achievements

 

 

2.2.1. Germ Cell Cancer

 

Prof. Schmoll started his first research in Medical Oncology in 1973 when he investigated - as the first investigator of the new compound - ifosphamide in refractory cancer, in particular in testicular cancer. He first identified the high efficacy of ifosfamide and thereafter he developed ifosfamide- and cisplatin-  based combinations. For this purpose he received as the first investigator in Europe Cisplatinum from the NCI, followed by the development of the Cisplatin/Ifosfamide-based combinations (VIP/PEI, Vbl/I/P, Vbl/BlM/I, etc.), parallel to and partially also in cooperation with Dr. Einhorn’s group in US. For this purpose he founded the Testicular Cancer Study Group, which represented the first german national multidiciplinary cooperative trial group for clinical oncology in Germany, and was organized within the framework of the AIO.  With several subsequent large prospective randomized trials investigating key questions for all stages of early and late germ cell cancer, including high dose salvage chemotherapy, together with his group including Drs. Harstrick, Bokemeyer etc., and also the EORTC-GU-group, Prof. Schmoll has set worldwide standards for the systemic and combined modality treatment in early and advanced stages of testicular cancer-several of them still valid today. He was also instrumental part for the development of the European Prognostic Factor - classification for advanced germ cell cancer. 

Through building up this cooperative network in Germany, together with Austria, he not only defined the standard treatments through carefully planned and well performed prospective clinical trials, but also this type of interdisciplinary cooperation and clinical science development in German speaking countries. Finally, he developed the European Germ Cell Cancer Consensus Group (EGCCCG) and - for the first time - defined the international standards for diagnosis and treatment of germ cell cancer in Europe and worldwide. The Consensus conference based guideline was published in AnnOncol as the first testis cancer guideline - one of the most cited papers in the journal. This was followed by the ESMO-Guideline-Consensus conference in 2008 and the  new ESMO-guideline, published in AnnOncol. 

 

2.2.2.Gastrointestinal Cancer

 

 

In the early 80ties, Prof. Schmoll has developed his second major field of clinical research, with esophageal, gastric, colon and rectal cancer. Through the development of national and international interdisciplinary trial-groups, Prof. Schmoll and his group, including Drs. Stahl, Wilke, Koehne, and later Grothey and Arnold, major new standards for several GI-cancer had been defined by his work. 

2.2.2.1 Gastric cancer 

Beyond new chemotherapy regimen, his group developed the basis for the principle of neo-adjuvant, preoperative chemotherapy, followed by secondary surgery, in locally advanced gastric cancer - an approach, which formed the basis for the current worldwide standard  treatment. 

 
2.2.3. Colon cancer 

2.2.3.1 Advanced Colorectal cancer 

For colon cancer, together with the EORTC GI group, Prof. Schmoll  developed sequential trials on first-line treatment in advanced colorectal cancer, beginning with the “AIO Schedule” (infusional 5-FU/folinic acid - which competed for long time with the French “De-Gramont-Schedule”), one of the n standard Oxaliplatin-combinations, and in the following all types of Capecitabin based protocols +/- targeted drugs, eg. Bevacizumab, Cetuximab and Cediranib.. These trials have defined new and worldwide standards, eg. the re-use of Bevacizumab -line, maintenance treatment, the development of 4-drug-combinations, or new trials designs, eg. the “MODUL trial” to overcome the time and resource problem for investigation of multiple and new targeted drugs. In addition, very early in the 8oties, his group (E. Schmoll) developed the combination of systemic chemotherapy + intraarterial chemoembolization/chemotherapy via arteria hepatica, as a multimodal approach in liver-limited advanced colorectal cancer, as well as the modality of chemoembolization for hepatocellular cancer. 

2.2.3.2. Early stage colon cancer 

In early stages of colon cancer, Prof. Schmoll has developed the current and future standard of adjuvant chemotherapy with XELOX in stage III disease by a worldwide large randomized trial (XELOXA); furthermore through translational analyses, this group has shown the high relevance of a molecular prognostic and potentially predictive molecular marker (DPD-expression) with the potential to select the adjuvant treatment more precisely (DPD expression). 

2.2.3.3. Locally advanced rectal cancer

For locally advanced rectal cancer, Prof. Schmoll co-developed the preoperative chemo-radiation with 5FU +/-Folinic acid. This work resulted finally in recent large international EORTC trial (PETACC 6) to investigate the additional role of oxaliplatin for pre- and post-op treatment of locally advanced rectal cancer, as one of the 2  ever performed phase III trials for this question. 

2.2.4. Development of sequential high dose chemotherapy  

Prof. Schmoll had developed as the first investigator worldwide the approach of sequential high dose chemotherapy, using hematopoetic stem cells for each sequential cycle of intermediate/high dose combination chemotherapy, for 4 – 5 cycles – a strategy which has been adopted for the high dose treatment for several tumor types.

 Further relevant clinical research was performed in neuro-/endocrine tumors, CUP-syndrom, and sarcoma; for example, the most recent prospective randomized trial is going to be presented at ASCO 2016 and will define a new standard for second-line treatment of advanced soft tissue sarcoma. 

2.3. Preclinic Research

 2.3.1 Tumor biology

Parallel to his clinical work and clinical trials, Prof. Schmoll had run from 1975 through 2014 an experimental research laboratory for tumor biology, with particular research on chemo sensitivity/resistance-mechanism, in particular for targeted drugs, and inhibition of angiogenesis. The findings  have been used for the development of the explorative clinical phase I/IIa-trials.

2.3.2 Mesenchymal stem cells as tumor directed gen-carrier

More recently, the potentials use of genetically (lentiviral vector, transduction of “trail”) modified mesenchymal stem cells  for targeted application of death signals (trail) specifically to tumor cells, via mesenchymal stem cells trafficking to the tumor site and -cells, has been explored. This unique approach is currently further evaluated preclinically and potentially also clinically.