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Ten years and counting: Survival in stage IV metastatic squamous cell carcinoma of anal canal following radical treatment


 Department Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Correspondence Address:
Umesh Mahantshetty,
Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_118_18

 > Abstract 


A 60-year-old male ptient presented with a 2-month history of altered bowel habits and occasional bleeding per rectum. On evaluation, he was diagnosed with squamous cell carcinoma of the anal canal (SCCAC) with an isolated hepatic lesion in segment II estimated as 4.3 cm × 3.5 cm on ultrasound. Subsequent needle biopsy confirmed metastatic squamous cell carcinoma deposits. The final diagnosis was SCCAC, cT4N1M1 (Stage IV). The patient was offered radical intent treatment. As per institutional protocol, the patient received two cycles of induction cisplatin + 5fluorouracil (FU) followed by chemo-radiation. 5FU and mitomycin C was given concurrently with irradiation. The primary and metastatic sites were irradiated using 6 MV photons on helical tomotherapy using conventional fractionation. Fluorodeoxyglucose positron emission tomograph-computed tomography performed 4 months after treatment completion showed a complete metabolic and morphological response. As of the date of writing, the patient is alive and disease free, 10 years after treatment with no long term sequelae.

Keywords: Anal canal carcinoma, chemoradiation, oligometastasis



How to cite this URL:
Maulik S, Hande V, Engineer R, Mahantshetty U. Ten years and counting: Survival in stage IV metastatic squamous cell carcinoma of anal canal following radical treatment. J Can Res Ther [Epub ahead of print] [cited 2019 Oct 19]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=264213




 > Introduction Top


Squamous cell carcinoma of the anal canal (SCCAC) is a rare malignancy of the gastrointestinal tract with predominantly locoregional relapse pattern. Extrapelvic metastases at diagnosis are seen in <10% of patients.[1] Common sites of extrapelvic metastases are the liver, lungs, and the para-aortic nodes. Many patients with distant metastases have an indolent disease course.[2]

Institutional series report median survival of around 2 years after treatment of anal carcinoma with hepatic metastases.[3],[4] The metastatic site was treated with either resection or radiofrequency ablation.

Historically, radiation therapy as a definitive therapy for hepatic lesions was not feasible owing to respiratory motion and limited radiation tolerance of hepatic parenchyma. The advances in radiation technology have now made it possible to overcome these obstacles.

Patient selection, dose-response relationships, fractionation schedules, safety parameters, and treatment techniques for definitive radiation to hepatic lesions are areas of ongoing research.[4]


 > Case Report Top


A 60-year-old -male with no known comorbidities, presented with a 2-month history of altered bowel habits and painless bleeding per rectum.

On examination, his general condition was good, with no obvious signs of anemia or lymphadenopathy. On per-rectal examination, the patient had a hard fixed ulceroproliferative growth on the anterior wall starting 1 cm from the anal verge extending superiorly to 5 cm. Sphincter tone was normal. Baseline hemogram, liver function tests, renal function tests, serum electrolytes, and chest X-ray were within normal limits. Biopsy of the lesion was suggestive of squamous cell carcinoma. Ultrasonography and computed tomography (CT) scan of the abdomen revealed anorectal mass infiltrating prostate and a 4.5 cm × 3.5 cm focal lesion in segment II of the liver suspicious of metastasis with no enlarged pelvic/para-aortic lymphadenopathy. Fine-needle cytology of this lesion was suggestive of metastatic squamous cell carcinoma. Relevant photomicrographs of fine-needle aspiration cytology of the liver lesion and rectal biopsy are shown in [Figure 1].
Figure 1: Photomicrograph of biopsy from primary rectal lesion (right) and fine-needle aspiration cytology from liver lesion (left) Photomicrograph of biopsy from primary rectal lesion (right) and fine-needle aspiration cytology from liver lesion (left)

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A final diagnosis of SCCAC, cT4N1M1 (Hep), and (Stage IV) was made. The patient was discussed in a multi-disciplinary tumor board meeting. The consulting surgeon declined to perform metastasectomy n view of isolated hepatic metastasis; the patient was offered radical intent treatment.

The patient received two cycles of induction chemotherapy with cisplatin 20 mg/sqm D1–5 and infusional 5-fluorouracil (FU) 650 mg/sqm D1-D5 for two cycles 3 weeks apart. The patient underwent intensity modulated radiation therapy (IMRT) using 6MV photons with helical tomotherapy from 8/4/08-14/5/08, 5 days a week. Concurrent chemotherapy with mitomycin-C 15 g/sqm D1 and infusional 5-FU 650 mg/sqm from D1-D5 and D21-D25.

Simulation contrast-enhanced CT (CECT) with thin slices (2.5 mm) was done, with patient supine in a polyurethane foam cushion. positron emission tomography – CT (PET-CT) coregistration with planning CECT images was performed In the absence of definitive guidelines on appropriate margins, combined clinical target volume + internal target volume margin of 15 mm to the gross tumor volume as defined on planning CECT and baseline PET-CT was deemed appropriate in view of spatial uncertainties of PET being compounded by the respiratory motion of the liver. An additional margin of 7 mm was added as margin for set up error. The final planning target volume (PTV) of the hepatic lesion had a volume of 173cc. The hepatic lesion was treated with conventional (2.2 Gy/#) fractionation to a dose of 55 Gy/25#. and 99% received a dose of at least 55 Gy/25#. The mean dose to the entire liver was 17.5 Gy.

Dose prescription to primary was 55.6 Gy/25# received by 99% of the PTV volume. Elective pelvic nodal volumes received 50 Gy/25# to 99% of the Nodal PTV. Daily image guidance was used with online megavoltage fan beam CT. With the translation and roll corrections suggested by automatic registration algorithm verified by the radiation oncologist.

The primary and liver lesion were both treated during the same treatment session.

Representative views of color dose wash are presented in [Figure 2].
Figure 2: Radiation dose color wash view

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The patient developed Grade 2 skin reactions, Grade 2 lower gastrointestinal toxicity, and Grade 1 genitourinary toxicity during treatment (radiation therapy oncology group toxicity grading).

An fluorodeoxyglucose PET-CT was performed 4 months after completing therapy, which showed a complete metabolic and morphological response. At last follow-up (July 2018), the patient remains disease-free 10 years posttreatment and is asymptomatic without signs of late toxicity.


 > Discussion Top


The burden of (metastatic) disease is primarily a surrogate of disease biology, which is probably the strongest prognosticator of outcomes. Patients with the upfront limited metastatic disease are a challenge to oncologic insight, since the trajectory of disease evolution (and thus disease biology) is unknown, unlike, for example, a treated patient with limited relapse after a prolonged disease-free interval.

Some patients with upfront metastasis can be treated with definitive intent with the hope of not only delaying relapse and possibly improving survival but also with a real chance of “cure” in the traditional sense.

Pushing the (dose) envelope on the traditional definition of a “curative” setting is the current mandate.

Aggressive and minimally morbid locoregional intervention for appropriately selected patients is complementary to the evolving role of novel immunological therapies for metastatic disease.[5]

Patients in the “gray zone” for aggressive radical management versus palliative treatment can be selected for radiation therapy, which is non-invasive, and thus acceptable, convenient and safe for the patient as well as feasible and effective for a range of lesion sites and sizes. Both conventional and hypo-fractionated regimens remain valid options: For example, we have used “conventional” image-guided-IMRT in the absence of advanced motion management techniques and robust data for hypofractionation (at the time) with a conventional dose fractionation schedule to treat a hepatic metastasis with curative results without evidence of toxicity. The relatively superficial location of the lesion was also favorable for achieving dose constraints.

The interested reader is referred to a good review article on the technical aspects of liver radiation.[6]

As a final point, the prognostic value of early PET-CT is to be noted. In our patient, a complete metabolic response was observed at 4 months posttreatment, which predicted a favorable long-term outcome.[7] Role of interval imaging in predicting better long-term outcome needs further exploration.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Boman BM, Moertel CG, O'Connell MJ, Scott M, Weiland LH, Beart RW, et al. Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer 1984;54:114-25.  Back to cited text no. 1
    
2.
Bilimoria KY, Bentrem DJ, Rock CE, Stewart AK, Ko CY, Halverson A, et al. Outcomes and prognostic factors for squamous-cell carcinoma of the anal canal: Analysis of patients from the national cancer data base. Dis Colon Rectum 2009;52:624-31.  Back to cited text no. 2
    
3.
Pawlik TM, Gleisner AL, Bauer TW, Adams RB, Reddy SK, Clary BM, et al. Liver-directed surgery for metastatic squamous cell carcinoma to the liver: Results of a multi-center analysis. Ann Surg Oncol 2007;14:2807-16.  Back to cited text no. 3
    
4.
Almaghrabi MY, Supiot S, Paris F, Mahé MA, Rio E. Stereotactic body radiation therapy for abdominal oligometastases: A biological and clinical review. Radiat Oncol 2012;7:126.  Back to cited text no. 4
    
5.
Sharabi AB, Tran PT, Lim M, Drake CG, Deweese TL. Stereotactic radiation therapy combined with immunotherapy: Augmenting the role of radiation in local and systemic treatment. Oncology (Williston Park) 2015;29:331-40.  Back to cited text no. 5
    
6.
Crane CH, Koay EJ. Solutions that enable ablative radiotherapy for large liver tumors: Fractionated dose painting, simultaneous integrated protection, motion management, and computed tomography image guidance. Cancer 2016;122:1974-86.  Back to cited text no. 6
    
7.
Grigsby PW. FDG-PET/CT: New horizons in anal cancer. Gastroenterol Clin Biol 2009;33:456-8.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2]



 

 
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