- Email: [email protected]
In Reply to Eapen
International Journal of
Radiation Oncology biology
physics
www.redjournal.org
COMMENTS Victor Despeignes, the Forgotten Pioneer of Radiation Oncology In Regard to Foray To the Editor: I write to congratulate the journal and Dr Foray, in particular, regarding the article “Victor Despeignes, the forgotten pioneer of radiation oncology” (1). Dr Foray has successfully woven the threads of commercial innovation, theories of cancer etiology, rapid adoption of emerging technologies, and provision of individualized patient care into an intriguing, historical, forensic treatise. The beautiful clinical description by Dr Despeignes of the patient’s findings of a tender epigastric mass and its subsequent transient but dramatic response to low-dose radiation therapy brings to mind the unerringly true colloquialism “plus c¸a change.” Assuming that this was a primary cancer within the epigastrium (rather than metastatic to that region), the post hoc clinical diagnosis of lymphoma seems sound. What is particularly compelling is the antecedent background of the creative scientific tension prevalent at that time between the parasitical-microbial and cellular theories of carcinogenesis. While the latter theory subsequently gained prominence and supplanted the former as the dominant concept in cancer etiology, this very first case of clinical radiation therapy likely dealt with a microbially derived cancer! With a focus on likely primary cancers that might present with an epigastric mass, it is illuminating to note that a primary hepatoma of the left lobe of the liver, a primary Mucosa Associated Lymphoid Tissue (MALT) gastric lymphoma, and a primary gastric adenocarcinoma are very much considered to be due to infectious microbes (2). Indeed, in 2016, an expanding list of microbe-derived cancers includes tumors of the oropharynx, nasopharynx, cervix, anal canal, skin, and hematopoietic system. Finally, underscoring the pivotal role of microorganisms in human disease, Dr Despeignes died of gastric ulcer complications, an entity currently understood to be infectious in etiology. Past is indeed prologue! Libni Eapen, MD The Ottawa Hospital Cancer Centre Radiation Oncology Ottawa, Ontario, Canada http://dx.doi.org/10.1016/j.ijrobp.2016.08.019
References 1. Foray N. Victor Despeignes, the forgotten pioneer of radiation oncology. Int J Radiat Oncol Biol Phys 2016;96:717-721. 2. Doorakkers E, Lagergren J, Engstrand L, et al. Eradication of helicobacter pylori and gastric cancer: A systematic review and metaanalysis of cohort studies. J Natl Cancer Inst 2016;108:djw132.
In Reply to Eapen To the Editor: I warmly thank the author of this letter for his interest in my article about Victor Despeignes (1, 2). I fully agree with him: it is true that, in addition to a certain serendipity and some diagnosis errors (2 colleagues of Despeignes confirmed that his patient suffered from stomach cancer [3]), 2 incredible coincidences must be highlighted. First, the tumor was very radiosensitive, which permitted Despeignes to report “a considerable decrease in its volume” after X-ray treatment (3). This was not so clear in the treatments described by Grubbe and Voigt (1). Second, as mentioned in the letter, mucosa-associated lymphoid tissue lymphoma can be caused by bacterial infections (4). Hence, mucosa-associated lymphoid tissue lymphoma is an example of cancer showing that the “parasitic theory,” so popular in 1896, was not entirely irrelevant. In the letter I deliberately focused on Victor Despeignes and his work: I did not provide further details about the patient of Despeignes, Euge`ne-Constant Colliat (1). Colliat was a confectioner who invested in weaving machines in Les Echelles (5) because this village is surrounded by strong streams whose waterpower was necessary for viscose production. (Structurally similar to cotton, viscose is a semisynthetic fiber also called artificial silk or rayon, extracted from wood and extensively used in clothing industry.) At the end of the 19th century, the viscose industry flourished in the region situated between Lyon and Grenoble, including Les Echelles. At this time, the production of 1000 kg viscose per day required 2000 kg sodium hydroxide, 1500 kg sulfuric acid, 550 kg carbon sulfur, and 2400 m3 of water per day (6). Consequently, as in the pulp and paper industry, viscose workers were exposed to a number of
Int J Radiation Oncol Biol Phys, Vol. 96, No. 4, pp. 919e924, 2016 0360-3016/$ - see front matter Crown Copyright Ó 2016 Published by Elsevier Inc. All rights reserved.
920
Comments
hazardous sulfur and chlorine compounds. To date, there is a large body of evidence that chronic exposure to these compounds significantly increases the risk of occupational lymphomas (7-9). Besides, the bad working conditions and the emergence of numerous diseases were at the origin of the first strikes and trade unions in the silk industry. One of the most famous characters of this period was a women, Lucie Baud, a trade unionist who was a contemporary of Despeignes and Colliat (6, 10). Hence, in addition to the possible microbial origin, a chemical origin may also be evoked for explaining the tumor of the Despeignes’s patient. Besides, these two hypotheses are not exclusive. The first tumor treated by X rays could also have been occupational. As mentioned in the letter, a microbial origin can also be evoked to explain the gastric ulcer of Despeignes. Despeignes, as Director of Hygiene for the city of Chambery for 30 years, may have manipulated hazardous chemicals as well. However, intense analyses of infected samples and micro-organism cultures were more likely responsible for the disease of Despeignes. I thank the author for the citation of Shakespeare at the end of his letter: it is really appropriate! However, the words that come immediately after the citation in The Tempest also fit our case and give us some responsibilities to better consider the works of the pioneers: “., what to come, In yours and my discharge.” Nicolas Foray, PhD Institut National de la Sante´ et de la Recherche Me´dicale Unite Mixte de Recherche 1052 Radiobiology Group Cancer Research Centre of Lyon Lyon, France http://dx.doi.org/10.1016/j.ijrobp.2016.08.021
References 1. Foray N. Victor Despeignes, the forgotten pioneer of radiation oncology. Int J Radiat Oncol Biol Phys 2016;96:717-721. 2. Foray N. Despeignes, the forgotten pioneer of radiation oncology. Int J Radiat Oncol Biol Phys 2016;96:919. 3. Despeignes V. Observation concernant un cas de cancer de l’estomac traite´ par les rayons roentgen. Lyon Med 1896;82:428-430. 4. Park JB, Koo JS. Helicobacter pylori infection in gastric mucosaassociated lymphoid tissue lymphoma. World J Gastroenterol 2014; 20:2751-2759. 5. Foray N. Victor Despeignes (1866-1937): How a hygienist became the first radiation oncologist. Cancer Radiother 2013;17:244-254. 6. Pinton A. La soie artificielle a` Lyon. Les E´tudes Rhodaniennes 1930;6: 229-250. 7. International Agency for Research on Cancer. Wood, leather and some associated industries. IARC Monogr Eval Carcinog Risks Hum 1981;25. 8. International Agency for Research on Cancer. Dry cleaning, some chlorinated solvents and other industrial chemicals. IARC Monogr Eval Carcinog Risks Hum 1995;63. 9. Tore´n K, Persson B, Wingren G. Health effects of working in pulp and paper mills: Malignant diseases. Am J Ind Med 1996;29:123-130. 10. Perrot M. Me´lancolie Ouvrie`re. Paris: Grasset; 2012.
International Journal of Radiation Oncology Biology Physics
Proton Therapy: More Questions Than Answers In Regard to Schlocker and Corn Lord, we know what we are, but know not what we may be. Ophelia in Hamlet, Act 4, Scene 5, by William Shakespeare To the Editor: The structure of public health masks the true costs of healthcare delivery, because it is considered a sunken investment, leading to chronic funding shortages. Cost shifting has become the pivot, with ballooning of administrative costs and modest gains in efficiency and the quality of deliverables (1). The editorial by Schlocker and Corn is instructive in this light (2). A narrow focus on specialization leads to better outcomes with a reduction of medical errors. These become more meaningful when measured by quality of life and better functional outcomes than by survival alone. The dice is, however, loaded heavily in favor of insurance payers who benefit from shielded positive competition, to stymie genuine medical innovation (3). Likewise, policy planners are confronted with opaque and myopic choices if seen from the perspective of evidence-based medicine. Particle therapy provides a distinctive treatment that delivers unique value to selected patients, although the benefits are unlikely to accrue in the short term. A major transition is required, with initial public funding, to accelerate the development of an ecosystem of technology providers coupled with universal health insurance (4). A positive spin off would be to nurture technological innovations in basic research. The driving down of costs with these efforts would provide an impetus for appropriate health-seeking behavior in the community. This would also require a radical overhaul of the “free healthcare mindset” to the co-pay model to ensure equitable participation of patients and healthcare providers. Good politics is bad economics, however. An integrated approach for healthcare delivery in communities with an emphasis on the preventive aspects of healthcare will improves measurable outcomes, even with heterogeneous patient inputs. This incorporates the full cycle of continuum care for sustainability in the long term. Over a period of time, concentrated volumes in integrated healthcare set up would boost meaningful and measurable cost reductions, including favorable patient outcomes (5). A consortium model will bring forth several organizational, team, and individual barriers that need to be overcome, including competing interests from a multitude of stakeholders. A multidisciplinary tumor board, as envisaged in the concept document, is likely to face significant ethical and moral challenges in defining patient appropriateness, because every patient selected for radiation therapy
Radiation Oncology biology
physics
www.redjournal.org
COMMENTS Victor Despeignes, the Forgotten Pioneer of Radiation Oncology In Regard to Foray To the Editor: I write to congratulate the journal and Dr Foray, in particular, regarding the article “Victor Despeignes, the forgotten pioneer of radiation oncology” (1). Dr Foray has successfully woven the threads of commercial innovation, theories of cancer etiology, rapid adoption of emerging technologies, and provision of individualized patient care into an intriguing, historical, forensic treatise. The beautiful clinical description by Dr Despeignes of the patient’s findings of a tender epigastric mass and its subsequent transient but dramatic response to low-dose radiation therapy brings to mind the unerringly true colloquialism “plus c¸a change.” Assuming that this was a primary cancer within the epigastrium (rather than metastatic to that region), the post hoc clinical diagnosis of lymphoma seems sound. What is particularly compelling is the antecedent background of the creative scientific tension prevalent at that time between the parasitical-microbial and cellular theories of carcinogenesis. While the latter theory subsequently gained prominence and supplanted the former as the dominant concept in cancer etiology, this very first case of clinical radiation therapy likely dealt with a microbially derived cancer! With a focus on likely primary cancers that might present with an epigastric mass, it is illuminating to note that a primary hepatoma of the left lobe of the liver, a primary Mucosa Associated Lymphoid Tissue (MALT) gastric lymphoma, and a primary gastric adenocarcinoma are very much considered to be due to infectious microbes (2). Indeed, in 2016, an expanding list of microbe-derived cancers includes tumors of the oropharynx, nasopharynx, cervix, anal canal, skin, and hematopoietic system. Finally, underscoring the pivotal role of microorganisms in human disease, Dr Despeignes died of gastric ulcer complications, an entity currently understood to be infectious in etiology. Past is indeed prologue! Libni Eapen, MD The Ottawa Hospital Cancer Centre Radiation Oncology Ottawa, Ontario, Canada http://dx.doi.org/10.1016/j.ijrobp.2016.08.019
References 1. Foray N. Victor Despeignes, the forgotten pioneer of radiation oncology. Int J Radiat Oncol Biol Phys 2016;96:717-721. 2. Doorakkers E, Lagergren J, Engstrand L, et al. Eradication of helicobacter pylori and gastric cancer: A systematic review and metaanalysis of cohort studies. J Natl Cancer Inst 2016;108:djw132.
In Reply to Eapen To the Editor: I warmly thank the author of this letter for his interest in my article about Victor Despeignes (1, 2). I fully agree with him: it is true that, in addition to a certain serendipity and some diagnosis errors (2 colleagues of Despeignes confirmed that his patient suffered from stomach cancer [3]), 2 incredible coincidences must be highlighted. First, the tumor was very radiosensitive, which permitted Despeignes to report “a considerable decrease in its volume” after X-ray treatment (3). This was not so clear in the treatments described by Grubbe and Voigt (1). Second, as mentioned in the letter, mucosa-associated lymphoid tissue lymphoma can be caused by bacterial infections (4). Hence, mucosa-associated lymphoid tissue lymphoma is an example of cancer showing that the “parasitic theory,” so popular in 1896, was not entirely irrelevant. In the letter I deliberately focused on Victor Despeignes and his work: I did not provide further details about the patient of Despeignes, Euge`ne-Constant Colliat (1). Colliat was a confectioner who invested in weaving machines in Les Echelles (5) because this village is surrounded by strong streams whose waterpower was necessary for viscose production. (Structurally similar to cotton, viscose is a semisynthetic fiber also called artificial silk or rayon, extracted from wood and extensively used in clothing industry.) At the end of the 19th century, the viscose industry flourished in the region situated between Lyon and Grenoble, including Les Echelles. At this time, the production of 1000 kg viscose per day required 2000 kg sodium hydroxide, 1500 kg sulfuric acid, 550 kg carbon sulfur, and 2400 m3 of water per day (6). Consequently, as in the pulp and paper industry, viscose workers were exposed to a number of
Int J Radiation Oncol Biol Phys, Vol. 96, No. 4, pp. 919e924, 2016 0360-3016/$ - see front matter Crown Copyright Ó 2016 Published by Elsevier Inc. All rights reserved.
920
Comments
hazardous sulfur and chlorine compounds. To date, there is a large body of evidence that chronic exposure to these compounds significantly increases the risk of occupational lymphomas (7-9). Besides, the bad working conditions and the emergence of numerous diseases were at the origin of the first strikes and trade unions in the silk industry. One of the most famous characters of this period was a women, Lucie Baud, a trade unionist who was a contemporary of Despeignes and Colliat (6, 10). Hence, in addition to the possible microbial origin, a chemical origin may also be evoked for explaining the tumor of the Despeignes’s patient. Besides, these two hypotheses are not exclusive. The first tumor treated by X rays could also have been occupational. As mentioned in the letter, a microbial origin can also be evoked to explain the gastric ulcer of Despeignes. Despeignes, as Director of Hygiene for the city of Chambery for 30 years, may have manipulated hazardous chemicals as well. However, intense analyses of infected samples and micro-organism cultures were more likely responsible for the disease of Despeignes. I thank the author for the citation of Shakespeare at the end of his letter: it is really appropriate! However, the words that come immediately after the citation in The Tempest also fit our case and give us some responsibilities to better consider the works of the pioneers: “., what to come, In yours and my discharge.” Nicolas Foray, PhD Institut National de la Sante´ et de la Recherche Me´dicale Unite Mixte de Recherche 1052 Radiobiology Group Cancer Research Centre of Lyon Lyon, France http://dx.doi.org/10.1016/j.ijrobp.2016.08.021
References 1. Foray N. Victor Despeignes, the forgotten pioneer of radiation oncology. Int J Radiat Oncol Biol Phys 2016;96:717-721. 2. Foray N. Despeignes, the forgotten pioneer of radiation oncology. Int J Radiat Oncol Biol Phys 2016;96:919. 3. Despeignes V. Observation concernant un cas de cancer de l’estomac traite´ par les rayons roentgen. Lyon Med 1896;82:428-430. 4. Park JB, Koo JS. Helicobacter pylori infection in gastric mucosaassociated lymphoid tissue lymphoma. World J Gastroenterol 2014; 20:2751-2759. 5. Foray N. Victor Despeignes (1866-1937): How a hygienist became the first radiation oncologist. Cancer Radiother 2013;17:244-254. 6. Pinton A. La soie artificielle a` Lyon. Les E´tudes Rhodaniennes 1930;6: 229-250. 7. International Agency for Research on Cancer. Wood, leather and some associated industries. IARC Monogr Eval Carcinog Risks Hum 1981;25. 8. International Agency for Research on Cancer. Dry cleaning, some chlorinated solvents and other industrial chemicals. IARC Monogr Eval Carcinog Risks Hum 1995;63. 9. Tore´n K, Persson B, Wingren G. Health effects of working in pulp and paper mills: Malignant diseases. Am J Ind Med 1996;29:123-130. 10. Perrot M. Me´lancolie Ouvrie`re. Paris: Grasset; 2012.
International Journal of Radiation Oncology Biology Physics
Proton Therapy: More Questions Than Answers In Regard to Schlocker and Corn Lord, we know what we are, but know not what we may be. Ophelia in Hamlet, Act 4, Scene 5, by William Shakespeare To the Editor: The structure of public health masks the true costs of healthcare delivery, because it is considered a sunken investment, leading to chronic funding shortages. Cost shifting has become the pivot, with ballooning of administrative costs and modest gains in efficiency and the quality of deliverables (1). The editorial by Schlocker and Corn is instructive in this light (2). A narrow focus on specialization leads to better outcomes with a reduction of medical errors. These become more meaningful when measured by quality of life and better functional outcomes than by survival alone. The dice is, however, loaded heavily in favor of insurance payers who benefit from shielded positive competition, to stymie genuine medical innovation (3). Likewise, policy planners are confronted with opaque and myopic choices if seen from the perspective of evidence-based medicine. Particle therapy provides a distinctive treatment that delivers unique value to selected patients, although the benefits are unlikely to accrue in the short term. A major transition is required, with initial public funding, to accelerate the development of an ecosystem of technology providers coupled with universal health insurance (4). A positive spin off would be to nurture technological innovations in basic research. The driving down of costs with these efforts would provide an impetus for appropriate health-seeking behavior in the community. This would also require a radical overhaul of the “free healthcare mindset” to the co-pay model to ensure equitable participation of patients and healthcare providers. Good politics is bad economics, however. An integrated approach for healthcare delivery in communities with an emphasis on the preventive aspects of healthcare will improves measurable outcomes, even with heterogeneous patient inputs. This incorporates the full cycle of continuum care for sustainability in the long term. Over a period of time, concentrated volumes in integrated healthcare set up would boost meaningful and measurable cost reductions, including favorable patient outcomes (5). A consortium model will bring forth several organizational, team, and individual barriers that need to be overcome, including competing interests from a multitude of stakeholders. A multidisciplinary tumor board, as envisaged in the concept document, is likely to face significant ethical and moral challenges in defining patient appropriateness, because every patient selected for radiation therapy