August - October 2018
Nutritional Status During Head and Neck Cancer Treatment
Vlad C. Sandulache, M.D., Ph.D.
Oct. 22 - Oct. 26, 2018
Specific question: What is the optimal strategy for enteral supplementation during and following treatment completion for head and neck cancer?
Patients with advanced stage head and neck cancer (HNC) generally present with significant reductions in quality of life at the time of diagnosis. This is particularly true for those patients with oral cavity, oropharyngeal or laryngeal disease which results in substantial impairment of speaking, swallowing and breathing. A significant percentage of patients with advanced disease generally present with varying degrees of malnutrition and a substantial plurality manifest cancer cachexia. Knowing that multi-modality treatment for advanced stage head and neck cancer can often exacerbate dysphagia (at least in the short term), clinicians often struggle with whether or not to recommend prophylactic gastrostomy placement as a means of enteral support during and following treatment. At the heart of this dilemma are two competing factors. On the one hand, active swallowing during treatment has conclusively been linked to improved post treatment function. On the other hand, active swallowing during treatment can be challenging for many patients; the absence of enteral support can potentially further jeopardize a tenuous nutritional status.
In 2017, Brown et al. reviewed data from 269 HNC patients treated with curative intent and stratified patients using a detailed risk assessment instrument which accounted for disease site, nutritional status and treatment selection. The instrument proved highly effective at identifying patients (deemed “high risk”) which benefited from prophylactic gastrostomy placement and found that oropharyngeal site and T stage were critical drivers of gastrostomy need during treatment along with malnutrition. Interestingly, the same group reported new data in 2018. They observed that within their own institution, adherence to this risk instrument dropped from 89% in 2010 to 60% in 2015 due to a variety of factors including introduction of newer radiation techniques and targeted agents as alternatives to conventional chemotherapy. For the time period of the study, adherence had decreased to nearly 50%, allowing for a direct comparison of patients which underwent prophylactic gastrostomy to patients which did not despite being considered “high-risk” using the instrument. This prospective study demonstrated less weight loss among patients who underwent prophylactic gastrostomy and a greater incidence of unplanned admissions in the no gastrostomy group; 43% of patients which did not undergo prophylactic gastrostomy required a reactive feeding tube and/or lost more than 10% of body weight.
These two studies from the same group of authors highlight the challenge for clinicians trying to develop rational, data driven approaches to this vexing clinical dilemma. Along with other studies they support the nutritional value of prophylactic gastrostomy, particularly for patients with advanced oropharyngeal disease. However, they also make it clear that implementation and sustenance of institutional algorithms remains challenging.
Brown TE, Banks MD, Hughes BGM, Lin CY, Kenny LM, Bauer JD. Comparison of Nutritional and Clinical Outcomes in Patients with Head and Neck Cancer Undergoing Chemoradiotherapy Utilizing Prophylactic versus Reactive Nutrition Support Approaches. J Acad Nutr Diet. 2018 Apr;118(4):627-636. PMID: 27986517
Brown TE, Wittholz K, Way M, Banks MD, Hughes BG, Lin CY, Kenny LM, Bauer JD. Investigation of p16 status, chemotherapy regimen, and other nutrition markers for predicting gastrostomy in patients with head and neck cancer. Head Neck. 2017 May;39(5):868-875. PMID: 28230929
Vlad C. Sandulache, M.D., Ph.D.
Oct. 1 - Oct. 5, 2018
Specific question: What is the ultimate utility of sentinel node biopsy for cutaneous melanoma?
Cutaneous melanoma remains one of the deadliest cancers in the United States, in large part due to its high propensity for regional (nodal basins) and distant metastasis. Head and neck cutaneous melanoma presents significant challenges for treating clinicians due to complex nodal metastatic patterns and the complex anatomy involved in addressing the nodal disease. Therefore, it is critical to know as accurately as possible when lymphadenectomy is required as well as the optimal extent of surgery required in order to minimize treatment related morbidity.
In 2014, Morton et al. published the final report of MSLT-I, a trial designed to evaluate the value of sentinel node biopsy (SNB) for melanoma. This trial provided much of the evidence used to incorporate SNB into professional organization guidelines throughout the US. The primary positive findings of the study was that SNB increased disease free survival for intermediate thickness melanoma (HR 0.76) and thick melanoma (HR 0.70) compared to observation, along with melanoma-specific survival (HR 0.56) for intermediate thickness melanoma (but not for thick melanoma). Although a landmark study, MSLT-1 does suffer from significant limitations. The most important one is failure to meet the primary outcome measure of improved overall survival. Additional limitations of the study include extensive subgroup analysis, a complex statistical analysis of failure time and no significant evaluation of treatment-related morbidity.
In 2017, MSLT-II followed MSLT-I and reported data on the value of completion nodal dissection for patients with a positive SNB. After randomizing nearly 2000 patients to completion dissection vs observation, the authors failed to detect an improvement in melanoma specific survival following completion dissection. A small improvement in regional control was reported. Of note, metastases were identified in nearly 12% of patients enrolled in the dissection group and were strongly associated with recurrence. These data provide critical information regarding the diagnostic limitations of SNB.
Sentinel node biopsy is routinely utilized at most academic centers throughout the US for intermediate and thick cutaneous melanoma, including head and neck melanoma. For most clinicians, it represents an important adjunct to high resolution anatomic imaging in appropriately stratifying patient risk of recurrence or distant metastasis. Nevertheless, it is important to critically assess the MSLT-I and MSLT-II data when counseling patients regarding the utility and morbidity of both SNB and completion neck dissection.
Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, Jahkola T, Bowles TL, Testori A, Beitsch PD, Hoekstra HJ, Moncrieff M, Ingvar C, Wouters MWJM, Sabel MS, Levine EA, Agnese D, Henderson M, Dummer R, Rossi CR, Neves RI, Trocha SD, Wright F, Byrd DR, Matter M, Hsueh E, MacKenzie-Ross A, Johnson DB, Terheyden P, Berger AC, Huston TL, Wayne JD, Smithers BM, Neuman HB, Schneebaum S, Gershenwald JE, Ariyan CE, Desai DC, Jacobs L, McMasters KM, Gesierich A, Hersey P, Bines SD, Kane JM, Barth RJ, McKinnon G, Farma JM, Schultz E, Vidal-Sicart S, Hoefer RA, Lewis JM, Scheri R, Kelley MC, Nieweg OE, Noyes RD, Hoon DSB, Wang HJ, Elashoff DA, Elashoff RM. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017 Jun 8;376(23):2211-2222. PMID: 28591523
Sladden M, Zagarella S, Popescu C, Bigby M. No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report. Br J Dermatol. 2015 Mar;172(3):566-71. PMID: 25776246
Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Puleo CA, Coventry BJ, Kashani-Sabet M, Smithers BM, Paul E, Kraybill WG, McKinnon JG, Wang HJ, Elashoff R, Faries MB; MSLT Group. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014 Feb 13;370(7):599-609. PMID: 24521106
Vlad C. Sandulache, M.D., Ph.D.
Aug. 20 - Aug. 24, 2018
Specific question: What is the relationship between Hashimoto’s thyroiditis and primary lymphoma of the thyroid?
First identified more than a century ago, Hashimoto’s thyroiditis (HT) represents a chronic lymphocytic thyroiditis which manifests as enlargement of the thyroid gland secondary to lymphocyte infiltration accompanied by chronic deterioration of thyroid function and eventually clinical hypothyroidism. Although most studies suggest a rate of Hashimoto’s thyroiditis in the United States in the range of 0.5-2% some pathologic and cytologic analyses have shown that up to 10% of patients with thyroid nodules can exhibit evidence of subclinical HT. Although the primary goal of clinical management of HT is to address the loss in thyroid function through hormonal replacement, HT has been linked to an increased risk of primary thyroid lymphoma (PTL), a deadly malignancy which presents a difficult diagnostic challenge.
Clinical manifestation of PTL can include rapid growth of a thyroid nodule, often in the context of previous thyroid enlargement and thyroid dysfunction (i.e. HT) with associated compressive symptoms. It is important to note however, that this presentation is nearly identical to that of anaplastic thyroid cancer (ATC) a disease with a very different pathophysiology, requiring different treatment algorithms and associated with poor survival. This is further complicated by the diagnostic challenges associated with differentiating HT from PTL and ATC via fine needle aspiration (FNA). Watanabe and colleagues conducted the largest and most comprehensive recent analysis to date and identified a rate of PTL in the context of HT of ~0.5%. Consistent with other smaller studies, the two most common PTL subtypes were diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma. Treatment for PTL in this series consisted primarily of radiation and chemotherapy, with surgery used primarily as a diagnostic procedure. Survival for the series exceeded 85% at 5 years.
Although an unusual manifestation of thyroid disease, PTL, particularly in the context of HT must remain within the clinical differential for rapidly enlarging thyroid masses and should be incorporated into surveillance algorithms for patients with HT.
Watanabe N, Noh JY, Narimatsu H, Takeuchi K, Yamaguchi T, Kameyama K, Kobayashi K, Kami M, Kubo A, Kunii Y, Shimizu T, Mukasa K, Otsuka F, Miyara A, Minagawa A, Ito K, Ito K. Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24553 patients with Hashimoto's disease. Br J Haematol. 2011 Apr;153(2):236-43. PMID: 21371004
Unknown Primary Squamous Cell Carcinoma of the Head and Neck
Vlad C. Sandulache, M.D., Ph.D.
Aug. 13 - Aug. 17, 2018
Specific question: What are the outcomes associated with treatment of carcinoma of unknown primary (CUP) of the head and neck?
The increasing frequency of oropharyngeal squamous cell carcinoma (OPSCC) associated with the human papilloma virus (HPV) has increasingly highlighted an old dilemma for clinicians caring for patients with head and neck cancer: carcinoma of unknown primary (CUP). Traditionally, CUP was thought to arise most frequently in the oropharynx. Today, with an ever increasing number of patients at risk for development of HPV-associated OPSCC (HPV+ OPSCC), the likelihood of small primary tumors generating bulky nodal disease that is readily identifiable on clinical exam and imaging has increased. Over the two decades, imaging (anatomic and metabolic) has begun to play an increasing role in the pre-treatment staging of OPSCC and in the planning of non-invasive treatment regimens (i.e. chemo-radiation). The widespread introduction of positron emission tomography (PET) throughout the United States provides a very useful tool for clinicians dealing with a potential CUP. Nevertheless, even in the modern era, approximately 2-5% of new head and neck cancer diagnoses will constitute a CUP.
Geltzeiler et al. (2017) describe the increasing role of transoral robotic surgery (TORS) in the management of CUP. In a relatively large series of patients, the authors demonstrate that TORS can augment exam under anesthesia and traditional laryngoscopy, and reduce the rate of CUP by nearly 75%. This is consistent with previous smaller studies, and suggests that TORS will likely maintain an important role in future diagnostic and staging algorithms for CUP. Kamal et al. (2018) provide recent data, primarily from the era of intensity modulated radiation therapy (IMRT), on clinical outcomes for those patients which retain a diagnosis of CUP despite extensive pre-treatment investigation. Overall, the data generated by this experienced, high-volume group are highly encouraging. Five-year disease free survival for CUP exceeded 90% and overall survival exceeded 80% for the entire cohort of 260 patients. Although a significant fraction of patients underwent gastrostomy placement (42%) prior to or during treatment, less than 10% of patients exhibited significant late term radiation associated dysphagia.
CUP will likely remain a significant clinical entity for the near future, fueled in part by the epidemic increase in HPV-associated OPSCC. Although the disease can be challenging for clinicians and patients alike, current treatment regimens retain very high efficacy which is reassuring.
Geltzeiler M, Doerfler S, Turner M, Albergotti WG, Kubik M, Kim S, Ferris R, Duvvuri U. Transoral robotic surgery for management of cervical unknown primary squamous cell carcinoma: Updates on efficacy, surgical technique and margin status. Oral Oncol. 2017 Mar;66:9-13. PMID: 28249654
Kamal M, Mohamed ASR, Fuller CD, Sturgis EM, Johnson FM, Morrison WH, Gunn GB, Hutcheson KA, Phan J, Volpe S, Ng SP, Ferrarotto R, Frank SJ, Skinner HD, Rosenthal DI, Garden AS. Outcomes of patients diagnosed with carcinoma metastatic to the neck from an unknown primary source and treated with intensity-modulated radiation therapy. Cancer. 2018 Apr 1;124(7):1415-1427. PMID: 29338089