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Published on February 8, 2021 by Aviram Mizrachi

Cutaneous Malignancies in the Organ Transplant Population

Case

A 68 y/o man with a history of kidney transplantation on Tacrolimus and prednisone treatment.

Several months prior to his presentation he underwent excision of a Rt temple skin lesion by a plastic surgeon. Pathology revealed a 4 mm SCC with evidence of PNI and free surgical margins. No further treatment or follow-up was recommended.

The patient presents now after noticing a weakness of Rt eyebrow for the last two months. He was seen at the Ophthalmology clinic and diagnosed with complete paralysis of the Rt temporal branch of CN-VII. In addition, there was a 2 cm firm subcutaneous painless mass on the Rt temple, deep to the surgical scar. Biopsy of the Rt temple lesion showed SCC. The patient was then referred to the head and neck clinic for further evaluation and treatment. There were no additional findings on physical examination and imaging studies did not show evidence of regional or distant disease (Figures 1, 2).

Figure 1
Figure 2: PET-CT

 

 

 

 

 

 

Risk of recurrence or metastases

The above case depicts a patient with a high risk for disease recurrence and/or metastases due to chronic immunosuppression. A recent review summarizes the role of the immune system in cutaneous SCC (Figure 3). In this paper the authors illustrate the effect of immunosuppressive drugs on several carcinogenic mechanisms including DNA repair, synergism with UV-related DNA damage, angiogenesis and invasiveness.  The NCCN guidelines address the group of high-risk patients with skin SCC and specify the risk factors that warrant close follow-up. Pay attention to “Area H” that includes the “Mask areas” of the face and is considered a high-risk feature (Figure 4).

Management

Every attempt should be made to achieve complete excision of the primary lesion with negative margins. Modification or reduction of immunosuppression should be considered and consulting the appropriate discipline (nephrologist, hepatologist etc.) is strongly encouraged. Adjuvant radiation may be recommended in cases of perineural involvement of large nerves. However, it should be noted that the definition of large nerves by AJCC 8th edition for skin SCC of the head and neck is above 0.1 mm and most nerves deep to the dermis are above 0.1 mm. Moreover, the survival benefit of adjuvant radiation following complete resection of the primary lesion remains unclear (Figure 5).

Outcomes

Several studies addressed the differences in survival outcomes between immunosuppressed and immunocompetent patients with skin SCC. A recent multi-center study reported on 67 immunosuppressed patients, most of them solid organ recipients, and compared them with 138 immunocompetent patients (Figure 8). They found better progression free survival and locoregional control in the immunocompetent patients group. However, no difference in overall survival between the two groups was noted. Another study by Ritter et al. compared 177 solid organ recipients with 177 immunocompetent patients with skin SCC. They found a significantly higher recurrence rate and worse overall survival in the solid organ recipients group (Figure 6).

Checkpoint inhibitors 

Immunocompromised patients have been traditionally excluded from the major clinical trials on checkpoint inhibitors. Solid organ recipients and patients with chronic viral infections (HIV, HBV, HCV) are considered poor candidates for checkpoint inhibitors due to the risk of allograft rejection and disease flare-up respectively. A multi-center European study reported on 46 patients treated with anti-PD-1/PD-L1 agents. Of them 6 were solid organ recipients and the remaining had chronic viral infections. They concluded that while patients with chronic viral infection may be safely treated with anti-PD-1/PD-L1 drugs, in solid organ recipients the risk of allograft rejection needs to be carefully weighed against the benefit of immunotherapy (Figure 7).

 

“CONCLUSION: Patients with HIV or hepatitus B/C infection treated with anti-PD-1/PD-L1 immunotherapy may respond to treatment without increased toxicity. Given the risk of graft rejection in solid organ transplant patients and also the potential for response, the role of anti-PD-1/PD-L1 immunotherapy needs to be carefully considered.”

 

Another study from MD Anderson Cancer Center reported on 37 solid organ recipients treated with checkpoint inhibitors. They found that 41% of patients experienced allograft rejection with a median time to rejection of 21 days from the initiation of immunotherapy. Furthermore, patients with allograft rejection had a significantly worse overall survival (Figure 8).

There is certainly a need for prospective trials in order to optimize the use of checkpoint inhibitors in immunosuppressed patients. A recently opened trial is enrolling kidney transplant recipients with advanced cancers, with an aim to treat them with Tacrolimus, Nivolumab and Ipilimumab. Additional details on this topic and the trial can be found in the following link:

https://ascopost.com/issues/march-10-2020/immune-checkpoint-inhibitors-in-solid-organ-transplant-recipients/

References

  • Bottomley MJ, Thomson J, Harwood C, Leigh I. The Role of the Immune System in Cutaneous Squamous Cell Carcinoma. Int J Mol Sci. 2019 Apr 24;20(8):2009. doi: 10.3390/ijms20082009. PMID: 31022866; PMCID: PMC6515307.
  • National Comprehensive Cancer Network. Squamous Cell Skin Cancer (Version 2.2020). https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf
  • Manyam BV, Garsa AA, Chin RI, Reddy CA, Gastman B, Thorstad W, Yom SS, Nussenbaum B, Wang SJ, Vidimos AT, Koyfman SA. A multi-institutional comparison of outcomes of immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for cutaneous squamous cell carcinoma of the head and neck. Cancer. 2017 Jun 1;123(11):2054-2060. doi: 10.1002/cncr.30601. Epub 2017 Feb 7. PMID: 28171708.
  • Ritter A, Badir S, Mansour M, Segal Z, Ad-El D, Bachar G, Shpitzer T, Popovtzer A, Mizrachi A. Solid organ transplantation worsens the prognosis of patients with cutaneous squamous cell carcinoma of the head and neck region-Comparison between solid organ transplant recipients and immunocompetent patients. Head Neck. 2020 Nov 27. doi: 10.1002/hed.26546. Epub ahead of print. PMID: 33247523.
  • Tio M, Rai R, Ezeoke OM, McQuade JL, Zimmer L, Khoo C, Park JJ, Spain L, Turajlic S, Ardolino L, Yip D, Goldinger SM, Cohen JV, Millward M, Atkinson V, Kane AY, Ascierto PA, Garbe C, Gutzmer R, Johnson DB, Rizvi HA, Joshua AM, Hellmann MD, Long GV, Menzies AM. Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection. Eur J Cancer. 2018 Nov;104:137-144. doi: 10.1016/j.ejca.2018.09.017. Epub 2018 Oct 20. PMID: 30347289.
  • Abdel-Wahab N, Safa H, Abudayyeh A, Johnson DH, Trinh VA, Zobniw CM, Lin H, Wong MK, Abdelrahim M, Gaber AO, Suarez-Almazor ME, Diab A. Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature. J Immunother Cancer. 2019 Apr 16;7(1):106. doi: 10.1186/s40425-019-0585-1. Erratum in: J Immunother Cancer. 2019 Jun 24;7(1):158. PMID: 30992053; PMCID: PMC6469201.
  • Bio
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Aviram Mizrachi

Aviram Mizrachi

Dr. Aviram Mizrachi is a surgeon-scientist at the Department of Otolaryngology – Head and Neck Surgery of Rabin Medical Center in Israel. He has an active research laboratory focusing on tumor and radiation biology in head and neck cancer as well as targeted drug delivery. Furthermore, he investigates both radiation and chemotherapy mechanisms of action and their effect on tumor and normal tissue including the utility of novel radio-sensitizing and radio-protective agents. In addition, Dr. Mizrachi conducts clinical research on outcomes in head and neck, skin and thyroid cancers.
Aviram Mizrachi

Latest posts by Aviram Mizrachi (see all)

  • Cutaneous Malignancies in the Organ Transplant Population - February 8, 2021
  • AHNS Basic Science/Translational Newsletter Vol 2 - April 24, 2020

Published on January 27, 2021 by AHNS Webmaster

Myers’ Family Summer Travel Fellowship in Otolaryngology Application is Open

 

Myers’ Family Diversity Summer Travel Fellowship in Otolaryngology for under-represented minority medical students 

This program is sponsored by the American Head and Neck Society Research and Education Foundation, thanks to the very generous contributions of Dr. Eugene Myers and Dr. Jeffrey Myers, as well as other AHNS donors.  It is intended to expose an under-represented minority medical student to the field of Head and Neck surgery specifically and Otolaryngology in general.

 

A grant of $5,000 will be awarded to a medical student to cover travel, lodging and food expenses for the summer experience.  This summer program offers the interested candidate the opportunity to work in a Department of Academic Excellence in Head and Neck Surgical Oncology that has an approved Fellowship Training Program from the Advanced Training Council of the AHNS.  Participants will be assigned to a clinical faculty mentor and will rotate on his or her clinical service and have the chance to participate in the care of Head and Neck Cancer patients in the outpatient setting, inpatient environment, as well as the operating room.  Summer fellows will also have the opportunity to perform basic, translational, clinical, or population based research under the guidance of a chosen/assigned research mentor.

 

The grant of $5,000 includes the recipients roundtrip airfare, cost to travel to the meeting, transportation to and from, food and hotel stay expenses at the AHNS Annual/International Meetings. At the AHNS Annual/International Meeting the student will share their Summer experience via PowerPoint presentation and can network with AHNS members. The Myers’ Family Summer Travel Fellowship in Otolaryngology FAQ page can be found by clicking here. 

To apply please click here to access the 2021 Myers’ Summer Travel Fellowship

 The application closes March 22, 2021 5PM EST. 

Published on January 25, 2021 by AHNS Webmaster

New Grant Opportunity from SU2C in Head and Neck Cancer: LOI Deadline March 22, 2021

Head and neck cancer is a blanket term used to describe several different types of cancers. About 65,000 new cases, not counting thyroid cancer, are diagnosed in the U.S. every year. A number of causes of these cancers have been identified, potentially offering new opportunities to screen for the cancers and create new treatments for patients.

For example, the incidence of head and neck squamous cell carcinoma in people with Fanconi anemia is 500- to 700-fold higher than in the general population. Additionally up to 70% of certain head and neck cancers are caused by human papillomavirus (HPV) infection. Genetic defects that cause Fanconi anemia, as well as genetic changes resulting from HPV infection, both adversely affect DNA repair systems, which can lead to cancer. This similarity provides investigators with different perspectives on a common problem and the opportunity to collaborate in new and innovative ways.

Head and neck cancers can appear in the nasal cavity, sinuses, lips, mouth, salivary glands, thyroid gland, throat or larynx. Experts estimate there are about 550,000 cases of various kinds of head and neck cancer diagnosed around the world each year, with 300,000 annual deaths due to the cancers. Research has also shown that Black people have higher incidence of head and neck cancer and a lower 5-year survival rate compared to white people. Black patients are also typically diagnosed with more advanced head and neck cancer.

To unlock potential new treatments, Stand Up To Cancer, with the generous support of the Fanconi Anemia Research Fund, the Farrah Fawcett Foundation, the American Head and Neck Society, and the Head and Neck Cancer Alliance, is offering up to $3.25 million in grants to fund research to find new treatments for head and neck cancer. The team will have a special focus on head and neck cancers associated with Fanconi anemia and HPV. Applicants will need to ensure that people from medically disadvantaged backgrounds are included in all phases of their proposed research.

Further information and a link to the application visit StandUpToCancer.org/HeadandNeck.

Published on January 15, 2021 by AHNS Webmaster

Apply Now for the AHNS FY2022 Fellowship Match

The 2022 Fellowship Match Application is Open

The AHNS currently accredits over 60 fellowship positions from 50 surgical programs in the U.S. and Canada. The application period has begun for fellowships commencing in July of 2022 – the application timeline is as follows:

Application Period: January 15, 2021 – March 1, 2021

Interview Period: March 1, 2021 – June 30, 2021

Ranking list opens for Programs and Applicants: July 1 – 12, 2021

Match results announced: Friday, July 16, 2021

For further information about the fellowships,
please visit the AHNS Website.

Start Your FY2022 Fellowship Application Now

If you have any questions about the online application, the participating programs or the process in general, please contact JJ Jackman in the AHNS Administrative Office at 310-437-0559 x154 or by email at [email protected].

Published on January 13, 2021 by AHNS Webmaster

USvsHPV Week – January 25-29, 2021

Dear AHNS Members,

Happy New Year!

We are excited to again be involved in the USvsHPV – Webinar Series to Promote Awareness About HPV-Related Diseases. The 2021 session will provide the latest updates on FDA’s approval of the HPV vaccine for oropharyngeal cancers, World Health Organization’s (WHO) formal adoption of the global strategy to eliminate cervical cancer, and American Cancer Society’s changes to the cervical cancer screening guidelines, among other important topics. Each 1-hour webinar is intended for health care providers, parents, patients, young leaders, students, and advocates who have an interest in the area of women’s health.

For more information, the Schedule of Events and to register for this event, visit the AHNS Website by clicking the banner below.

I hope you can attend!

Sincerely,

Michael G. Moore, MD
AHNS Cancer Prevention Service Chair

 

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