Month: June 2018

stereotatic radiosurgery after resection

Merkel Cell Carcinoma Treated with Wide Local Excision with or without Radiotherapy and Chemotherapy: A Multi-Institutional Retrospective Analysis

Morteza Dowlatshahi MD, Reza Shirazi MD, Ly Do MD, Tri Do MD, Arash Salari BS, Lawrence Huan MD, and Robert A. Kagan MD

———————————————————————————–

Purpose: The purpose of this study was to evaluate the treatment of Merkel cell carcinoma with or without radiotherapy and chemotherapy. In order to gain a better understanding of management and assess prognostic factors, data from 3 California cancer centers was pooled and retrospectively analyzed.

Materials and Methods: We reviewed 26 consecutive cases of Merkel cell carcinoma from June 2000 to October 2010. There were 16 male and 10 female patients. The majority of the cases involved the upper extremities (54%), followed by the head and neck (35%), and finally lower extremities (11%). No tumors were noted in the trunk. Twenty-seven percent of the patients presented with stage I disease (localized with a tumor <2 cm), 31% with stage II disease (localized with a tumor >2 cm), and 42% percent with stage III disease (nodal metastasis). No patients presented stage IV (distant metastasis). All patients were surgically treated with wide local excision and lymph node dissection when appropriate. Radiotherapy was administered with curative intent in 18 patients (69%). 6 patients (23%) additionally received radiotherapy after a recurrence. 2 patient (8%) did not receive radiotherapy at all. In addition, four patients were treated with chemotherapy.

Results: With an average follow-up time of 32 months, 10 patients (38%) had recurrent disease. The median time to recurrence was 8.8 months with a mean of 11.8 months. Although tumor size and site of presentation were not observed to be statistically significant, significant results were observed based on lymph node involvement and post-operative radiation therapy. Patients with positive lymph node status at the time of diagnosis had a statistically significant (P < 0.05) lower overall survival rate [mean 21 months] as compared to patients having no lymph node involvement [mean 44 months]. Also, the recurrence rate was 85% in patients treated with surgery alone as compared to 17% for surgery + adjuvant radiation (P < .05). Patients treated with chemotherapy were not statistically analyzed because the systemic effect of chemotherapy would have been less clear due to the small number of patients. 2 and 5-year survival rates were 70% and 53% respectively.

Conclusion: Adjuvant radiation therapy is recommended in all patients undergoing surgical management of MCC. Lymph node metastasis carries a dismal prognosis. Early detection is vital in the management of Merkel cell carcinoma.

Introduction

Merkel cell carcinoma (MCC) first described by Toker in 1972 is an aggressive cutaneous malignancy of neuroendocrine origin.¹ Due to the rarity of MCC, it is often misdiagnosed as basal cell carcinoma, squamous cell carcinoma, melanoma, angiosarcoma, or cutaneous lymphoma. Regardless, the incidence rate for Merkel cell carcinoma has been on the rise from 0.15 per 100,000 in 1986 to 0.6 per 100,000 in 2012.^2-3 This increase may be credited to many reasons, including increased clinical awareness, improved testing, and an increasing elderly population.^{2, 4-6} Environmental factors such as an increase in sun exposure have also been attributed to the increase in the malignancy. Immunocompromised patients exhibit higher rates of MCC.^{2, 7-8}

The danger in Merkel cell carcinoma is that the cancer is clinically aggressive. Tumors larger than 2 cm and clinically positive lymph nodes have revealed to have a poor prognostic outcome for recurrence.^{6-7, 9-11} The SEER results (2003) in the United States for five year survival of metastatic MCC is a poor 25%.⁶ Because of these various reasons more clinical awareness needs to be observed to this specific type of skin cancer.

However, due to the rarity of MCC, there is still a significant lack of information surrounding the best practices and outcomes. Experience gained from retrospective studies like this one can help the optimal treatment of these uncommon types of cancer. This article presents 26 consecutive cases that were treated with surgery, radiotherapy, and/or chemotherapy. We will evaluate the effectiveness of our different treatment options and compare our results to the literature. Survival and prognostic factors will be statistically analyzed and discussed.

Materials and Methods

Patients

Patients were identified searching the EMR databases of three California cancer centers. The databases were pooled for patients receiving treatment for Merkel cell carcinoma between June 2000 and October 2010. All patients who were included in the analysis had histologically confirmed MCC. (Further eligibility of patients? Metastatic, nonmetastatic, age? Other malignancies?)

 

Staging

Our study used the four-tier staging system developed by the Memorial Sloan-Kettering Cancer Center (MSKCC). A patient’s tumor was initially biopsied and clinically evaluated. If further testing was appropriate the adjacent lymph nodes were biopsied and a computer tomography (CT) of the chest, abdomen, and regional areas were performed. The MSKCC staging for MCC is consistent with the staging system used by the American Joint Committee on Cancer.¹² Another predominant staging system, proposed by Yiengpruksawan et al. was also found and both staging systems have been presented in Table 1 for clarity.¹³

Surgical Treatment

After positive biopsy the primary tumor was surgically removed by wide local excision. Adjacent lymph nodes were also clinically evaluated and biopsied when appropriate. Treatment after a positive lymph node was based on patient and treating physician preference. Various studies are suggesting a routine biopsy of the sentinel lymph node (SLNB) in MCC patients to detect a spread that would otherwise have been clinically undetected.^{11, 14-15} Due to the aggressive nature of MCC elective LN dissection (LND) with clinically negative lymph nodes are still being debated by surgical oncologists.^16-17

Radiation Therapy

Radiation therapy usually consisted of > 50 greys (Gy) of external-beam radiation for 5 days per week over a 5 to 6-week course. Radiation was administered to the primary tumor excision site and/or draining LN basin. In our study adjuvant RT is defined as RT to the primary tumor site and/or regional LN basin within 4 months of wide local excision and/or LN dissection.

Chemotherapy

Chemotherapy consisted of a platinum agent in combination with an etoposide. One patient’s chemotherapy regimen consisted of a platinum agent and an irenotecan. Treatment was administered for a total of 4 to 6 cycles over 6 to 8 weeks. Patients received chemotherapy as an adjuvant treatment or after a recurrence. ( What was the clinical indication for chemotherapy?)

Follow-Up

Patients were seen in the clinic every few months for 2 years and once or twice a year thereafter. Patients not followed in person were contacted by telephone. Recurrence was defined as a clinically or histologically discovered return of tumor. Recurrences were categorized as local, regional, or distant. The date of recurrence was defined as the first clinically positive account indicating the return of carcinoma. The time to recurrence was defined as the interval from the concluding date of therapy to the date of confirmed recurrent carcinoma.

Statistical Analysis

Statistical analysis was performed using the statistical software JMP (version 10 for PC; SAS Institute, Inc., Cary, NC). Log-Rank and Wilcoxon tests were used to statistically analyze survival time in the two different cohorts (patients receiving adjuvant RT and patients not receiving adjuvant RT). A chi-square analysis was used to examine the etiological differences of disease. Overall survival was determined by the Kaplan-Meier method. Patients who died during the course of the study were censored to not bias the outcome of analysis. P-values of < .05 were considered to be statistically significant.

Results

Patient Characteristics

Twenty-six patients with stage I through stage III MCC were clinically identified and treated within 4 months of diagnosis at the Cancer Care Institute of San Jose, Radiation Medical Group of California, and the Valley Medical Center of California. Table 2 lists patient demographic information, tumor/pathology, and follow-up information from our study population.

The median age of diagnosis was 78 years (range of 47 to 99 years). About 70% of our patients were over the age of 70. There was an overall male predominance with 16 male patients (62%) and 10 female patients (38%). An overwhelming majority of our patients were white, 23 patients (88%) and the remaining 3 patients (12%) were Hispanic.

The most common sites of occurrences were in sun-exposed areas: 8 (30%) in the head and neck region, 14 (54%) in the upper extremities, and 2 (8%) in the lower extremities. No tumors were found in the trunk region. The median size of tumor was 2.1cm with a range of 0.7cm-5.2cm. Two patients (8%) presented with no primary tumor.

Fifteen patients (58%) presented with clinically localized MCC [7 patients (27%) with clinical stage I disease and 8 patients (31%) with clinical stage II disease]. Eleven patients (42%) presented with clinical stage III disease. Final pathologic stage included 1 patient (4%) with stage IA disease, 6 patients (23%) with stage IB disease, 4 patients (15%) with stage IIA disease, 4 patients (15%) with stage IIB disease, 1 patient (4%) with IIIA disease, and 10 patients (38%) with IIIB disease. No patients presented with distant metastasis (stage IV).

Surgical Treatment

A wide local excision was performed on all patients presenting with a primary tumor (n=24, 2 patients presented without a primary tumor). 18 patients underwent a margin-negative excision while 6 patients had clinically positive margins. Of the 15 patients who presented with clinically negative lymph nodes, 5 patients elected to have a sentinel lymph node biopsy (SLNB) and 2 elected to have an optional lymph node dissection (LND). The remaining 8 patients had no further LN treatment or evaluation. Of the 11 patients who presented with clinically positive LN’s and no evidence of metastatic disease, all underwent total lymph node dissection (TLND).

Radiotherapy

Radiotherapy with curative intent was administered in 18 patients. In our cohort, 6 of 7 patients with stage I MCC and 5 of 8 patients with stage II MCC received adjuvant RT. 5 of 11 stage III patients received adjuvant RT to the draining lymph node basin in addition to the primary tumor site. An additional 2 stage III patients received adjuvant RT to the tumor bed only having presented with no primary tumor.

The median dose of adjuvant radiation to the primary tumor site was 5870 cGy with a range of 4000cGy-6040cGy. The average dose was about 5600 cGy. The median dose of adjuvant radiation to the LN bed was 5250 cGy with a range of 5000cGy-6000cGy. The average dose to the LN bed was about 5460 cGy.

Six of the 8 patients in the surgical group eventually received radiation after a recurrence. Their median dosage was 5500 cGy with a range of 5000 cGy – 7020 cGy. The average does for this group was 5840 cGy.

Chemotherapy

Chemotherapy was received by 4 of 26 patients. The median age was 74 years of age (range 60years-84years). Three of the 4 patients were stage III; the fourth patient was stage I. All patients received carboplatin or cisplatinum. Three patients received a concurrent etoposide and one patient received a concurrent irenotecan. Chemotherapy was received as an adjuvant therapy by two patients and as salvage therapy in two patients who experienced a recurrence.

At Last Follow-Up

The median follow-up time was 32 months (range of 4months-102months). At last follow-up 10 patients (38%) had recurrent disease. The median time to recurrence was 8.8 months with a mean of 11.8 months. Recurrence occurred locally in one patient, regionally in three, and distantly in three. One patient had a locoregional recurrence and two patients had a combination of regional and distant metastasis. The recurrence rate was 17% for surgery + adjuvant radiation as compared to 85% in patients treated with surgery alone. (p < 0.05). The effect of systemic chemotherapy on recurrence was not statistically analyzed because the outcome would be less clear as a result of the small number of patients (only four). Patients with positive lymph node status at the time of diagnosis had a statistically significant (P < 0.05) lower overall survival rate noted [mean 21 months] as compared to patients having no lymph node involvement [mean 44 months]. Gender, age, location, and tumor size were not statistically found to affect overall survival. The mean overall survival of the whole cohort was 3.1 years with 2 and 5-year survival rates of 70% and 53% respectively as summarized in Figure 1.

Discussion

MCC will typically present as a colored, painless, firm subcutaneous nodule with or without ulceration or telangiactasias.³ The lesion is often clinically mistaken and an acronym “AEIOU” has been proposed to raise awareness [Asymptomatic/lack of tenderness, Expanding rapidly (doubling in < 3 months), Immunosuppresion, Older than 50 years, Ultraviolet exposed skin site].⁴ There are many benign lesions though that can meet several of the conditions for the AEIOU acronym. To avoid confusion, suspicious lesions should always be biopsied.

MCC and other malignancies such as: small cell lung carcinoma, carcinoid tumors, malignant lymphoma, and small-cell melanoma share similar histological characteristics. MCC usually appears as a dermal tumor extending into the subcutaneous fatty tissue with the papillary dermis and adnexa usually being spared.^18-19 Further evaluation shows positive stains for epithelial and neuroendocrine markers, but negative stains for lymphoid and melanoma markers.^19-20 It has been hypothesized that MCC originates from a slow-acting pressure receptor within the skin. Increasing evidence suggests that malignant transformations occur in the pluripotent neuroendocrine stem cells within the dermis.^21-22

It is understood that MCC is generally a disease of elderly Caucasian individuals with a slight male predominance.^{2, 4, 6-7, 23} This observation is consistent with our results as a majority of our patients were white and male (88% and 62% respectively) with a median age of 78 years. Furthermore, patients with immunosuppresion have been reported to have an increased risk of MCC as compared to immunocompetent patients. ^24-25 In our study only one patient was immunosuppressed (CLL). Other possible risk factors are arsenic exposure and prior irradiation.^26-27 Recently, a polyomavirus [MCPyV] has been linked to Merkel cell carcinoma. Advanced research and the development of a specific monoclonal antibody has detected the polyomavirus currently in 97% of tumors.^28-29 With innovative research and increased detection further novel treatments can be discovered to treat this carcinoma. For example, in one study subcutaneous interferon-beta proteins were reported successfully in inducing apoptosis in MCC cells.³⁰

Unfortunately, due to the exceeding rarity of this tumor, there is a lack of definitive date  (data?) regarding MCC and its treatment. Combination therapies consisting of surgical excision, lymph node dissection, radiotherapy, and/or chemotherapy are commonly used. Wide local excision with negative margins is the preferred surgical intervention.^31-32 Bajetta et al. found margin status in surgically treated patients to be significantly (P < 0.001) associated with recurrence.³¹ A problem with MCC is that it regularly presents in the head and neck regions where clear margins are unattainable. Combination radiotherapy has proven effective in treating MCC tumors and controlling the rates of local recurrence.^{10, 32-36} In our study all patients (24) presenting with a primary tumor were treated with wide local excision. Of those 24, 6 (25%) had positive margins. Clear margins were not attained on these patients because clear margins were not surgically feasible in their presenting locations. Half of the six patients with positive margins were treated with adjuvant radiotherapy and experienced no recurrence. The other half of the six patients not receiving adjuvant radiotherapy all experienced a recurrence either locally, regionally, or distally. Overall in our study the recurrence rate was 17% for surgery + adjuvant radiation as compared to 85% in patients treated with surgery alone (P < .05). This leads to our recommendation that all patients with MCC be treated with adjuvant radiotherapy following surgical excision.

The most accurate predictor of prognosis is the involvement of regional lymph nodes. Given this information sentinel lymph node biopsy is gaining favor in determining the extent of disease and detecting microscopic metastases that may have gone clinically unnoticed.^11,15,17 As shown in Figure 2, patients in our study with positive lymph nodes had a statistically significant (P < 0.05) lower overall survival [mean 21 months] as compared to patients with no lymph node involvement [mean 44 months]. Our suggestion is every patient presenting with MCC be administered a SLNB to search the adjacent lymph nodes for microscopic disease. Due to the aggressive nature of this cancer complete lymph node dissection for clinically negative lymph nodes has proven beneficial for high-risk tumors such as those that are larger than 1.0cm, located in the head or neck, have a high mitotic rate, or tumors that have invaded the lymphatics or vasculature.^16,17,38 It is still being debated in the literature if a complete lymph node dissection is necessary in all MCC cases due to its high morbidity.³⁷

Chemotherapy does not have a clearly defined role in the treatment of MCC. One study advises chemotherapy for locally recurrent or advanced disease patients who have a history of good performance status.³⁹ In our study we treated 4 patients with chemotherapy: adjuvant therapy in 2 patients and salvage therapy in 2 patients. Three of these 4 patients were not cured by chemotherapy and at last follow-up were either alive with disease or dead of disease. To note, these three patients all had advanced disease (stage III) at time of presentation. The one patient who did respond well to chemotherapy had early stage disease (stage I) and was treated very aggressively (surgery, radiation, and chemotherapy). With such a small patient pool statistical analysis was not carried out on these four patients. Our hypothesis to why chemotherapy didn’t work in our three patients is it was administered after a recurrence or the possibility the right combination may not have been used. In the Tai et al. study ( notation?) cyclophosphamide/doxorubicin/ (or epirubicin)/vincristine combination +/- prednisone was the most commonly used regimen (47 patients) with the highest overall response rate of 75.7%.³⁹ Our patients were treated with a combination etoposide/cisplatin (or carboplatin). Tei et al. reported a 60% overall response in our combination, but regardless a statistically significant difference in effectivity was not noted between the two groups (P=.19).³⁹ Another hypothesis proposed by Garneski et al. explains chemotherapeutic ineffectiveness in MCC  could be due to the suppression of the immune system.⁴⁰ The immune system plays a large role in defending the host from the development and progression of MCC.^3,8,24-25 Due to these conflicting arguments the only way to truly confirm whether chemotherapy improves the results in high-risk MCC is to run a larger randomized study.

Conclusion

While our small study contributes to the data published about Merkel Cell carcinoma, there is still much left to be investigated with this aggressive malignancy. The results show early detection and combination therapies being a predictor of good prognosis. Based on our study, all patients presenting with MCC should be treated with wide local excision and be administered a SLNB to detect microscopic lymph node metastasis. In addition all patients should be treated with radiotherapy to the tumor bed and regional lymph nodes.

Table 1. Staging Systems for Patients with Merkel Cell Carcinoma^12-13

Staging System	Criteria
Memorial Sloan-Kettering Cancer Center TNM staging system
T
1	Primary tumor < 2cm
2	Primary tumor > 2cm
N
0	Negative regional lymph node involvement
1	Positive regional lymph node involvement
M
0	No evidence of distant metastatic disease
1	Presence of distant metastatic disease
Stage
I	T1, N0, M0
II	T2, N0, M0
III	Any T, N1, M0
IV	Any T, Any N, M1
Yiengpruksawan et al. three-tiered staging system
IA	Primary tumor < 2cm
IB	Primary tumor > 2cm
II	Regional lymph node metastasis
III	Distant metastases

Figure 1. Kaplan-Meier Curve for Overall Survival

Figure 2. Kaplan-Meier Curve for Overall Survival in Patients Presenting with Involved Lymph Nodes

Table 2. Patient Characteristics of the Patients Diagnosed with Merkel Cell Carcinoma (Cancer Care Institute of San Jose, Radiation Medical Group of California, and Valley Medical Center of California Health Databases, 2000-2010)

Characteristic	Number of Patients	Percentage
Median Age at Diagnosis: 78 years	26	100%
Gender
Male	16	62%
Female	10	38%
Ethnicity
White	23	88%
Hispanic	3	12%
Location of primary, n=26
Head and Neck	8	30%
Upper Extremity	14	54%
Lower Extremity	2	8%
Trunk	0	0%
No primary	2	8%
Primary tumor diameter, cm n=24
Median	2.1cm
Range	0.7cm-5.2cm
Stage at diagnosis per MSKCC system, n=26
I	7	27%
II	8	31%
III	11	42%
IV	0	0%

Table 3. Treatment Profiles of Patients Diagnosed with Merkel Cell Carcinoma in the Cancer Care Institute of San Jose, Radiation Medical Group of California, and Valley Medical Center of California Health Databases, 2000-2010

	Number of Patients	Percentage
Type of surgical resection, n=26
Wide Local Excision	24	92%
Total Lymph Node Dissection	11	42%
Adjuvant therapy
RT to Primary Site, Median Dosage 5870 cGy	18	69%
RT to LNB*, Median Dosage 5250 cGy	5	19%
RT+Chemotherapy	2	8%

*Lymph node Basin

References

1. Toker C. Trabecular carcinoma of the skin. Arch Dematol 1972; 105: 107-110.
2. Hodgson NC. Merkel cell carcinoma: Changing incidence trends. J Surg Oncol 2005; 89 (1): 1-4.
3. Jaeger T, Ring J, Andres C. Histological, immunohistological, and clinical features of Merkel cell carcinoma in correlation to Merkel cell polyomavirus status. J Skin Cancer 2012; 1: 1-5.
4. Heath M, Jaimes N, Lemos B, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol 2007; 58 (3): 375-381.
5. Scott MP, Helm KF. Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma. Am J Dermatopathol 1999; 21 (1): 16-20.
6. Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol 2003; 49 (5): 832-841.
7. Albores-Saavedra J, Batich K, Chable-Montero F, et al. Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population study. J Cutan Pathol 2010; 254: 465-475.
8. Rockville Merkel Cell Carcinoma Group. Merkel cell carcinoma: recent progress and current priorities on etiology, pathogenesis, and clinical management. J Clin Oncol 2009; 27 (24): 4021-4026.
9. Fields RC, Busam KJ, Chou JF, et al. Five hundred patients with Merkel cell carcinoma evaluated at a single institution. Ann Surg 2011; 254: 465-475.
10. Clark JR, Veness MJ, Gilbert R. Merkel cell carcinoma of the head and neck: Is adjuvant therapy necessary? Head Neck 2007; 29 (3): 249-257.
11. Gupta SG, Wang LC, Penas PF, et al. Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature. Arch Dermatol 2006; 142: 685-690.
12. Edge SB, Byrd DR, Compton CC, et al. American Joint Committee on Cancer: Cancer Staging Manual. New York: Springer, 2009.
13. Yiengpruksawan A, Coit DG, Thaler HT, et al. Merkel cell carcinoma: Prognosis and management. Arch Surg 1991; 126: 1514-1519.
14. Fang LC, Lemos B, Douglas J, et al. Radiation monotherapy as regional treatment for lymph node-positive Merkel call carcinoma. Cancer 2010; 116 (7): 1783-1790.
15. Hill AD, Brady MS, Coit DG. Intraoperative lymphatic mapping and sentinel lymph node biopsy for Merkel cell carcinoma. Br J Surg 1999; 86: 518-521.
16. Stokes JB, Graw KS, Dengel LT, et al. Patients with Merkel cell carcinoma tumors < 1.0 cm in diameter are unlikely to harbor regional lymph node metastasis. J Clin Oncol 2009; 27: 3772-3777.
17. Fields RC, Busam KJ, Chou JF, et al. Recurrence and survival in patients undergoing sentinel lymph node biopsy for merkel cell carcinoma: analysis of 153 patients from a single institution. Ann Surg Oncol 2011; 18 (9): 2529-2537.
18. McCardle TW, Sondak VK, Zager J, et al. Merkel cell carcinoma: pathologic findings and prognostic factors. Curr Probl Cancer 2010; 34 (1): 47-62.
19. Eng TY, Boersma MG, Fuller CD, et al. A comprehensive review of the treatment of Merkel cell carcinoma. Am J Clin Oncol 2007; 30 (6): 624-636.
20. Sarnaik AA, Lien MH, Nghiem P, et al. Clinical recognition, diagnosis, and staging of Merkel cell carcinoma, and the role of the multidisciplinary management team. Curr Probl Cancer 2010; 34: 38-46.
21. Tilling T, Moll I. Which are the cells of origin in Merkel cell carcinoma? J Skin Cancer 2013; [Epub ahead of print].
22. Calder KB, Smoller BR. New insights into Merkel cell carcinoma. Adv Anat Pathol 2010; 17 (3): 155-161.
23. Duprat JP, Landman G, Salvajoli JV, et al. A review of the epidemiology and treatment of Merkel cell carcinoma. Clinics 2011; 66 (10): 1817-1823.
24. Lanoy E, Engels EA. Skin cancers associated with autoimmune conditions among eldery adults. Br J Cancer 2010; 103 (1): 112-114.
25. Paulson KG, Iyer JG, Blom A, et al. Systemic immune suppression predicts diminished Merkel cell carcinoma specific survival independent of stage. J Invest Dermatol 2012; [Epub ahead of print].
26. Ho SY, Tsai YC, Lee MC, et al. Merkel cell carcinoma in patients with long-term ingestion of arsenic. J Occup Health 2005; 47 (2): 188-192.
27. Bertrand M, Mirabel X, Desmedt E, et al. Merkel cell carcinoma: A new radiation induced cancer? Ann Dermatol Venereol 2013; 140 (1): 41-45.
28. Arora R, Chang Y, Moore PS. MCV and Merkel cell carcinoma: a molecular success story. Curr Opin Virol 2012; 2 (4): 489-498.
29. Rodig SJ, Cheng J, Wardzala J, et al. Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus. J Clin Invest 2012; 122 (12): 4445-4453.
30. Nakajima H, Takaishi M, Yamamoto M, et al. Screening of the specific polyoma virus as diagnostic and prognostic tools for Merkel cell carcinoma. J Dermatol Sci 2009; 56 (3): 211-213.
31. Bajetta E, Celio L, Platania M, et al. Single-institution series of early-stage Merkel cell carcinoma: Long-term outcomes in 95 patients managed with surgery alone. Ann Surg Oncol 2009; 16 (1): 2985-2993.
32. Senchenjov A, Barnes SA, Moran SL. Predictors of survival and recurrence in the surgical treatment of Merkel cell carcinoma of the extremities. J Surg Oncol 2007; 95 (3): 229-234.
33. Veness M, Foote M, Gebski V, et al. The role of radiotherapy alone in patients with Merkel cell carcinoma: Reporting the Australian experience of 43 patients. Int J Radiat Oncol Biol Phys 2009; 78 (3): 703-709.
34. Kang SH, Haydu LE, Goh Ry, et al. Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma. Radiat Oncol 2012; [Epub ahead of print].
35. Veness MJ, Morgan GJ, Gebski V. Adjuvant locoregional radiotherapy as best practice in patients with Merkel cell carcinoma of the head and neck. Head Neck 2005; 27 (3): 208-216.
36. Jabbour J, Cumming R, Scolyer RA, et al. Merkel cell carcinoma: assessing the effect of wide local excision, lymph node dissection, and radiotherapy on recurrence and survival in early-stage disease—results from a review of 82 consevutive cases diagnosed between 1992 and 2004. Ann Surg Oncol 2007; 14 (6): 1943-1952.
37. Gonzalez RJ, Padhya TA, Cherpelis BS, et al. The surgical management of primary and metastatic Merkel cell carcinoma. Curr Probl Cancer 2010; 34 (1): 77-96.
38. Poulsen M. Merkel-cell carcinoma of the skin. Lancet Oncol 2005; 5 (10): 593-599.
39. Tai PT, Yu E, Winquist E, et al. Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. J Clin Oncol 2000; 18 (12): 2493-2499.
40. Garneski KM, Nghiem P. Merkel cell carcinoma adjuvant therapy: current data support radiation but not chemotherapy. J Am Acad Dermatol 2007; 57 (1): 166-169.

Orbital Lymphoma

IBT in patients with augmentation

Ly Do M.D. (1), Morteza Dowlatshahi M.D. (1), Zayd Parekh (2), Richard Trevino (3), Richard Eng M.D. (3), Karen Fann (3), Ngon Dinh (3), Raymond Lee M.D. (4), Charlene Lee M.D. (4), Tin Hla M.D. (4)

1. Cancer Care Institute, 200 Jose Figueres Ave #199, San Jose, CA 95116, 2. San Jose State University 3. Department of ENT, Regional Medical Center of San Jose, 200 Jose Figueres Ave, San Jose, CA 95116, 4. Department of Medical Oncology Regional Medical Center of San Jose, 200 Jose Figueres Ave, San Jose, CA 95116 

Objectives- LAHNSCC can be treated with concurrent chemoradiation or concurrent radiation with cetuximab.  Previous studies have suggested superior outcomes for LAHNSCC treated with radiation and cisplatin versus radiation and cetuximab (1-3). We compared outcomes amongst our cohort of patients who were treated with concurrent radiation therapy (RT) and cisplatin versus concurrent RT and cetuximab in a community hospital setting.

Methods- Retrospective analysis was performed on stage III and IV LAHNSCC patients treated at Cancer Care Institute from 01/97 to 08/17 with cisplatin (n=37) or cetuximab (n=11) with concurrent RT to 7000 cGy using 3DCRT or IMRT with image guidance. Patients included in this study had LAHNSCC of the oropharynx, hypopharynx, larynx, and oral cavity. Patient’s with metastatic disease at presentation were excluded. LRC, OS, and distant metastasis-free survival survival were then analyzed using the Kaplan Meier Method and Cox analysis tools.

Results-  3-year LRC for concurrent chemoradiation was 100% vs. 42% for cetuximab and radiation (P < 0.0001).  OS was found to be non-significantly different with 5-year OS of concurrent chemoradiation to be at 56% vs. 48%; for cetuximab and radiation (P = 0.6). 3 patients in the cetuximab treated group had successful salvage treatment with surgical resection. 2/3 of these patients required total laryngectomies. None of the patients treated with chemoradiation required salvage therapy. 2-year organ preservation rate for concurrent chemoradiation was 100% vs. 87.5% for cetuximab and radiation (P = 0.0047).

Conclusions- The data obtained from this retrospective analysis adds to a growing body of literature that suggests that RT with concurrent cisplatin may yield superior outcomes in comparison to concurrent cetuximab (1-3). In addition, our data suggests a higher quality of life with improved organ preservation rates associated with chemoradiation. Randomized phase III trials should be performed to validate these findings.

Frameless SRS

FRAMELESS STEREOTATIC RADIOSURGERY FOR BRAIN METASTASES USING FACE MASK IMMOBILIZATION

Ly Do, M.D.¹, Morteza Dowlatshahi, M.D.¹ ,Emeka Nchkwube, M.D.², Michael Le B.S.³, Ali Shirzadi, M.D.⁴, Chuong Le, M.D.⁵, Raymond Lee,M.D.⁶, Tin HLa, M.D.⁷, Lynne Bui, M.D.⁸, Peggy Lu, M.D.⁹.

¹Cancer Care Institute, 200 Jose Figueres Ave. # 199, San Jose, CA 95116, ² E&D Nchekwube, MD, INC 1825 Civic Center Dr. # 17, Santa Clara, CA 95050, ³University of South Carolina, Columbia, SC 29208, ⁴South Bay Brain and Spine, 2577 Samaritan Dr. #710, San Jose, CA 95124, ⁵Wave Neurology, 200 Jose Figueres Ave. #475, San Jose, CA 95116, ⁶Regional Medical Center Medical Oncology, 200 Jose Figueres Ave. # 245, San Jose CA 95116, ⁷Huan & HLa Medical Corporation, 200 Jose Figueres Ave. # 430, San Jose CA 95116, ⁸ Global Cancer Research Institute, Inc. 2242 Camden Ave. # 203, San Jose CA 95124, ⁹San Jose Medical Group, 227 N Jackson Ave, San Jose CA 95116

Purpose: To evaluate our experience of frameless stereotatic radiosurgery (SRS) using face mask immobilization in patients with brain metastases.

Methods and Materials:  15 patients with brain metastases (range, 1-3), were selected to undergo SRS.    Dose of SRS was 1,800 cGy – 2,500 cGy in 3 – 5 fractions.  All patients underwent MRI brain prior to treatment.  MRI of the brain was then fused to our CT simulation.  Gross tumor volume was expanded by 3mm to create the planning tumor volume.   All patients were immobilized using aquaplast face mask.  Follow-up magnetic resonance imaging (MRI) occurred on average between 1- 2 months post SRS.  Patients who had CNS metastases recurrences after SRS were treated with salvage whole brain radiation.

Result:  From June 2012 till April 2015, 6 out 15 patients died.  Two (13.3%) developed local recurrences at the treated sites, 4 (26.6%) developed new intracranial distant recurrences, and 9 (60%) were recurrence free.  The actuarial survival rates of local recurrence-free were 91% for 12 months and 72% for 24 months.  The actuarial survival rates of distant recurrence-free are 56% for 12 months and 42% for 24 months.   The actuarial overall survival rates were 70% for 12 months and 55% for 24 months.  WBRT was administered on 3 (20%) of the 15 patients.

Conclusion:   Our results on the use of frameless SRS are favorable to the literature.  This suggests the use of face mask immobilization would not lead to inferior outcomes in patients who require SRS for brain metastasis.  This may obviate the need for the more invasive and cumbersome immobilization techniques.  This would lead to increased convenience and comfort of the patient while ensuring similar efficacy and outcomes.

 

Figure 1. Local Recurrence Free Survival           Figure 2. Distant Recurrence Free Survivial             Figure 3. Overall Survival

 

 

 

Do T4 colon cancer abstract