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Theoretical study of CN chemisorbed on the Pd(111) surface
Cancer Immunology, Immunotherapy https://doi.org/10.1007/s00262-018-2208-y
LETTER TO THE EDITORS
“Pseudoprogression”: more than semantics Janice P. Dutcher1 Received: 11 June 2018 / Accepted: 11 July 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018
Dear Editors, I wish to comment on the recently published article, “Pushing the limits of immune-related response: a case of ‘extreme pseudoprogression’”, by AS Wong, et al. [1]. I take exception to categorizing this case as “pseudoprogression” following one dose of nivolumab, particularly due to the serious clinical deterioration that is described. Rather, I would categorize this as a case of “flare” following cessation of a potent angiogenesis inhibitor, followed by a nearly miraculous response to immunotherapy, particularly after so much prior therapy. This is a case report of a heavily pre-treated patient with widely metastatic renal cell cancer (RCC), having received 4 anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) as well as surgeries and radiation. His last systemic treatment was axitinib (4th systemic therapy), a very potent VEGFR-TKI, which was stopped after 7 months due to progression of disease. On the day that this drug was stopped, he received a single dose of nivolumab. The patient had multiple large metastases in the remaining right kidney, among multiple other sites (bone, liver, spleen, right adrenal, pancreas, peritoneum, lung and lymph nodes). Within 2 weeks of stopping axitinib, the patient developed acute renal failure from progression of the tumors in the kidney, as well as marked clinical deterioration with dyspnea, edema and a decline in performance status. This syndrome of rapid progression after stopping an antiVEGF agent is consistent with multiple reports of “flare” in patients with RCC who have stopped anti-VEGF TKIs as well as preclinical data demonstrating enhanced endothelial proliferation [2]. In view of the biology of RCC, in which This comment refers to the article available online at https://doi. org/10.1007/s00262-018-2167-3. * Janice P. Dutcher [email protected] 1
the loss of the von Hippel–Lindau tumor suppressor protein leads to the development of clear cell RCC, with interaction of hypoxia-inducible factor (HIF) and stimulation of growth by VEGF, as described by Kaelin [3], the clinical flare in RCC upon cessation of anti-VEGFR-TKI agents is presumed to be proliferative stimulation by excess circulating VEGF. Pseudoprogression after checkpoint inhibition (CPI), as described by Wolchok and Hodi was initially observed in melanoma and was characterized at the time of first evaluation, generally at 8–12 weeks after starting CPI [4]. The initial and subsequent descriptions of what was later defined as pseudoprogression, were of the early development of new lesions, but with overall increase of total disease burden of no more than 25%. Additionally, there was no description of significant clinical deterioration, but primarily radiologic progression. Subsequently, such patients, with less than or equal to 25% increase in tumor burden, demonstrated regression of both baseline and new lesions. Clinical deterioration was considered progression, even with immune-related response criteria. The clinical course of this patient is much more consistent with the rapid progression from unopposed VEGF stimulating tumor growth, and this may be particularly characteristic of RCC, given the VEGF-dependent biology, and the aggressive use of anti-VEGF therapy. Fortunately, the patient survived long enough to then, at 10 weeks, demonstrate clinical improvement from CPI therapy. It is also remarkable that this patient was capable of immune responsiveness, given four lines of systemic therapy as well as surgery and radiation. This case is educational from two aspects—(a) the demonstration of clinical progression flare after cessation of anti-VEGFR TKI, leading to renal failure and diffuse disease progression, and (b) delayed but significant response to immunotherapy despite multiple prior therapies. Thus, progression due to one mechanism, can be reversed by the implementation of a completely different mechanism of disease control.
Cancer Research Foundation of New York, 43 Longview Lane, Chappaqua, NY 10514, USA
13
Vol.:(0123456789)
Compliance with ethical standards Conflict of interest The author declares that she has no conflict of interest.
References 1. Wong AS, Thian Y-L, Kapur J, Leong C-N, Kee P, Lee C-T, Lee MB (2018) Pushing the limits of immune-related response: a case of “extreme pseudoprogression”. Cancer Immunol Immunother 67:1105–1111. https://doi.org/10.1007/s00262-018-2167-3
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Cancer Immunology, Immunotherapy 2. Ebos JML, Pili R (2012) Mind the Gap: Potential for rebounds during anti-angiogenic treatment breaks. Clin Cancer Res 18:3719–3721 3. Kaelin WG Jr (2007) The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res 13(2Pt2):680 s–684 s 4. Hodi FS, Ballinger M, Lyons B, Soria J-C, Nishino M, Tabernero, Powles T, Smith D, Hoos A, McKenna C et al (2018) ImmuneModified response evaluation criteria in solid tumors (imRECIST). J Clin Oncol 36:850–858
LETTER TO THE EDITORS
“Pseudoprogression”: more than semantics Janice P. Dutcher1 Received: 11 June 2018 / Accepted: 11 July 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018
Dear Editors, I wish to comment on the recently published article, “Pushing the limits of immune-related response: a case of ‘extreme pseudoprogression’”, by AS Wong, et al. [1]. I take exception to categorizing this case as “pseudoprogression” following one dose of nivolumab, particularly due to the serious clinical deterioration that is described. Rather, I would categorize this as a case of “flare” following cessation of a potent angiogenesis inhibitor, followed by a nearly miraculous response to immunotherapy, particularly after so much prior therapy. This is a case report of a heavily pre-treated patient with widely metastatic renal cell cancer (RCC), having received 4 anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) as well as surgeries and radiation. His last systemic treatment was axitinib (4th systemic therapy), a very potent VEGFR-TKI, which was stopped after 7 months due to progression of disease. On the day that this drug was stopped, he received a single dose of nivolumab. The patient had multiple large metastases in the remaining right kidney, among multiple other sites (bone, liver, spleen, right adrenal, pancreas, peritoneum, lung and lymph nodes). Within 2 weeks of stopping axitinib, the patient developed acute renal failure from progression of the tumors in the kidney, as well as marked clinical deterioration with dyspnea, edema and a decline in performance status. This syndrome of rapid progression after stopping an antiVEGF agent is consistent with multiple reports of “flare” in patients with RCC who have stopped anti-VEGF TKIs as well as preclinical data demonstrating enhanced endothelial proliferation [2]. In view of the biology of RCC, in which This comment refers to the article available online at https://doi. org/10.1007/s00262-018-2167-3. * Janice P. Dutcher [email protected] 1
the loss of the von Hippel–Lindau tumor suppressor protein leads to the development of clear cell RCC, with interaction of hypoxia-inducible factor (HIF) and stimulation of growth by VEGF, as described by Kaelin [3], the clinical flare in RCC upon cessation of anti-VEGFR-TKI agents is presumed to be proliferative stimulation by excess circulating VEGF. Pseudoprogression after checkpoint inhibition (CPI), as described by Wolchok and Hodi was initially observed in melanoma and was characterized at the time of first evaluation, generally at 8–12 weeks after starting CPI [4]. The initial and subsequent descriptions of what was later defined as pseudoprogression, were of the early development of new lesions, but with overall increase of total disease burden of no more than 25%. Additionally, there was no description of significant clinical deterioration, but primarily radiologic progression. Subsequently, such patients, with less than or equal to 25% increase in tumor burden, demonstrated regression of both baseline and new lesions. Clinical deterioration was considered progression, even with immune-related response criteria. The clinical course of this patient is much more consistent with the rapid progression from unopposed VEGF stimulating tumor growth, and this may be particularly characteristic of RCC, given the VEGF-dependent biology, and the aggressive use of anti-VEGF therapy. Fortunately, the patient survived long enough to then, at 10 weeks, demonstrate clinical improvement from CPI therapy. It is also remarkable that this patient was capable of immune responsiveness, given four lines of systemic therapy as well as surgery and radiation. This case is educational from two aspects—(a) the demonstration of clinical progression flare after cessation of anti-VEGFR TKI, leading to renal failure and diffuse disease progression, and (b) delayed but significant response to immunotherapy despite multiple prior therapies. Thus, progression due to one mechanism, can be reversed by the implementation of a completely different mechanism of disease control.
Cancer Research Foundation of New York, 43 Longview Lane, Chappaqua, NY 10514, USA
13
Vol.:(0123456789)
Compliance with ethical standards Conflict of interest The author declares that she has no conflict of interest.
References 1. Wong AS, Thian Y-L, Kapur J, Leong C-N, Kee P, Lee C-T, Lee MB (2018) Pushing the limits of immune-related response: a case of “extreme pseudoprogression”. Cancer Immunol Immunother 67:1105–1111. https://doi.org/10.1007/s00262-018-2167-3
13
Cancer Immunology, Immunotherapy 2. Ebos JML, Pili R (2012) Mind the Gap: Potential for rebounds during anti-angiogenic treatment breaks. Clin Cancer Res 18:3719–3721 3. Kaelin WG Jr (2007) The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res 13(2Pt2):680 s–684 s 4. Hodi FS, Ballinger M, Lyons B, Soria J-C, Nishino M, Tabernero, Powles T, Smith D, Hoos A, McKenna C et al (2018) ImmuneModified response evaluation criteria in solid tumors (imRECIST). J Clin Oncol 36:850–858