Table of Contents

Original articlesCan Metastatic lymph node ratio be used as an independent prognostic factor in Carcinoma tongue? ..............................................06V.M Bharath, P.G. Balagopal, Abraham George Nebu, A.V. Jayasudha, M. Iqbal Ahmed, Paul Sebastian

Synergistic Protective effect of Sickle Cell Trait and Blood Group-O on the risk of endemic Burkitt’s lymphoma.............................11Sagir G. Ahmed, Umma A. Ibrahim, Modu B. Kagu

Clinicopathological Spectrum of anaplastic Carcinoma of Thyroid – 5 year experience from a Tertiary Cancer Centre ......................17Pattamparambath Manjusha, Joseph Philip Kandathil, Sangeetha K. Nayanar, Joneetha Jones, Babu Sajith

investigating the relationship between psychological hardiness and resilience with depression in women with breast cancer .......23Mitra Tadayon, Saeideh Dabirizadeh, Kourosh Zarea, Naser Behroozi, Mohamad Hossin Haghighizadeh

Clinicopathological outcome of ovarian granulosa cell tumors ...............................................................................................................31Ehab Al-Rayyan, Maher Maaita, Omar Alelwan, Omar Taso, William Hadadin

anaplastic Carcinoma Thyroid - a review on the Management of this aggressive Cancer ..................................................................37Syed Afroze Hussain, S. Subbiah, M.S. Bharathiraja

Prevalence of Stomach Cancer in isfahan Province, iran .........................................................................................................................42Zahra Tolou Ghamari

accuracy of intraoperative frozen section evaluation of sentinel lymph node biopsy in breast cancer: Our experience in Bahrain ..........................................................................................................................................................................46Raed Almarzooq, Amal Alrayes, Ahmed Saeed, Hussain Abdulla

laparoscopy as a Primary investigatory Tool in Pediatric abdominal Masses .......................................................................................52Ossama M. Zakaria, Mohamed Yasser I Daoud, Tamer A. Sultan, Karam El Sayem, Hazem M. Zakaria, Amr M. El-Gibaly, Fouad M Sedky, Assma Al Taher, Hamed A Al Wadaani

Survival Outcome of Pulmonary Metastasectomy among Patients with Sarcoma and Colorectal Primary Cancers: a Single institute experience .....................................................................................................................................................................56Abdulrahman A. Alghamdi, Manar A. Hasabullah, Alhanouf I. Alhusani, Leema K. Alhussayen, Khawlah M. Fairaq, Samar S. Alsifri, Turki M. Al-Fayae

review articlesThe role of Surgery in Palliative Care of Cancer: a review .....................................................................................................................61Pankaj Kumar Garg, Aakanksha Goel

Case reportslife threatening bleeding from an osteonecrosis of the jaw: are bisphosphonates safe in irradiated head and neck cancer patients? .........................................................................................................................................................................72Tarek Assi, Ralph Chebib, Sara Lakiss, Joseph Kattan

right Temporal Brain Metastases arising Three years after Curative resection of Gastric Cancer: a Case report ...................................................................................................................................................................75Ayman Zaki Azzam, Mohammad Anas Dababo, Kareem Ayman Azzam, Meshal Almeshal, Tarek Mahmoud Amin

Conference Highlights/Scientific Contributions• NewsNotes............................................................................................................................................................................................78

• Advertisements .....................................................................................................................................................................................82

• ScientificeventsintheGCCandtheArabWorldfor2018 ..................................................................................................................83

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Survival After Pulmonary Metastasectomy in Sarcoma and Colorectal Primary Cancers, Abdulrahman A. Alghamdi, et. al.

Corresponding author: Turki M. Al-Fayae, MD, Princess Norah Oncology Center, Department of Adult Medical Oncology, King Saud bin Abdulaziz University

for Health Sciences, College of Medicine, Jeddah, Saudi Arabia, PO Box 9515, Jeddah 21423. Contact

No. +966568559996. Email: FayaeTM@ngha.med.sa

introductionMalignant metastasis of cancer cells from solid tumors

to distant organs remains a challenge to successful treatment and a major cause of cancer-related mortality.( 1) Lungs are one of the organs most commonly targetewd by metastasis, with between 30% and 55% of all cancer patients found to have pulmonary metastases on autopsy.(2,3) The prevalence of pulmonary metastases varies depending on many factors, such as the primary tumor site and its histology and size.(4)

abstract

Background: One of the most common organs targeted by metastatic malignancies are the lungs. In the field of surgical oncology, pulmonary metastasectomy (PM) is frequently performed for patients with pulmonary metastatic nodules secondary to specific primary tumors. This study aimed to evaluate survival and its predictors among patients with primary sarcoma or colorectal cancer who underwent PM at the Princess Norah Oncology Center, Jeddah, between 2007 and 2016.

Patients and methods: Sarcoma and colorectal cancer patients with isolated lung metastasis and who underwent PM in our institution between 2007 and 2016 were identified. Overall survival and possible survival predictors were assessed using log-rank test and multivariate analysis was implemented using Cox regression.

results: Thirty-eight patients (16 with colorectal cancer and 22 with sarcoma) were identified. The median follow-up duration was 26 months (range 0–88). A total

of 11 patients (28.9%) died during the follow-up period. The 5-year survival rates for patients who underwent PM with primary colorectal and sarcoma were 89% and 41%, respectively. Univariate analysis indicated that PM in patients with primary colorectal cancer was associated with longer overall survival (p value = 0.023) compared with PM with sarcoma. In the multivariate analysis, a metastatic lesion with size ≥ 15 mm and having primary colorectal cancer were the factors significantly associated with prolonged survival.

Conclusion: Our experience has shown a substantial 5-year survival benefit for patients with primary tumors of sarcomas and colorectal cancer who underwent a PM. A primary tumor of the colorectum and larger pulmonary metastases were associated with a better outcome. We recommend PM, following careful selection, for patients with pulmonary deposits secondary to a primary tumor of Colorectum or sarcoma.

Keywords: Pulmonary Metastasectomy, Survival Analysis, Sarcoma, Colorectal Cancer

Original Article

Survival Outcome of Pulmonary Metastasectomy among Patients with Sarcoma and Colorectal Primary Cancers:

a Single institute experienceAbdulrahman A. Alghamdi1,2, Manar A. Hasabullah1,2, Alhanouf I. Alhusani1,2, Leema K. Alhussayen1,3,

Khawlah M. Fairaq 1,4, Samar S. Alsifri1,5, Turki M. Al-Fayae1,2,6

1 King Abdullah International Medical Research Center, Riyadh, Saudi Arabia 2 King Saud bin Abdulaziz University for Health Sciences, College of Medicine, Jeddah, Saudi Arabia

3 Taibah University, College of Medicine, Madinah, Saudi Arabia 4 King Abdulaziz University, College of Medicine, Jeddah, Saudi Arabia

5 Ibn Sina National College, Jeddah, Saudi Arabia 6 Dept. of Adult Medical Oncology, Princess Norah Oncology Center, NGHA, Jeddah, Saudi Arabia

Colorectal cancer and sarcomas are among the common sources for pulmonary metastases.(5) In the case of colorectal cancer, the 5-year cumulative risk for lung metastasis is estimated to be 5.8%. (6) In contrast,

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pulmonary metastases occur in 20–50% of patients with soft-tissue sarcoma, and in 11–20% of patients with osteosarcoma at the time of initial diagnosis. (7- 10) However, there are no large population-based studies to determine the trend and incidence of pulmonary metastasis in patients with sarcoma.

As pulmonary metastases are usually initially asymptomatic, they tend to be detected incidentally or in late stages.( 5) Since the first successful pulmonary metastasectomy (PM) in 1944, it has been considered the mainstay of therapy for those patients with resectable pulmonary deposits. (11) Several studies since then have assessed survival and the related parameters. There is a noticeable variation in 5-year survival outcomes among patients with different primary tumors, such as sarcomas and epithelial carcinomas. For sarcomas, the 5-year survival rate is reported as 34% and 25% for bone and soft tissues, respectively. (12) For colorectal carcinoma (CRC), the most common of the epithelial carcinomas, 5-year survival is 27–68%. (13)

Careful pre-operative selection of patients who may benefit from PM is crucial. The basic prerequisites that candidates should meet are a completely controlled primary tumor, no extrapulmonary metastases, complete resectability of metastases, and tolerability to the procedure. (14) Other prognostic factors have been suggested to affect the overall outcome of this procedure, such as the primary tumor type, its location, length of disease-free interval, and number of metastases. (4, 15)

This study aimed to evaluate the survival outcomes and associated prognostic factors among patients with primary sarcoma or CRC who underwent PM at Princess Norah Oncology Center (PNOC), Jeddah, in the period between 2007 and 2016.

Patients and methodsA retrospective analysis was performed on all

patients with a histopathological diagnosis of either CRC or sarcoma, with proven metastasis to the lung. To be included, the candidates had also to undergo a surgical resection of that metastasis at PNOC during the period 2007–2016. PNOC is one of the leading cancer centers in Saudi Arabia (SA) and the biggest in the western region. It also serves a considerable number of patients from the western, northern, and southern regions of SA. The King Abdullah International Medical Research Center (KAIMRC) approved the study.

Data on patient demographics and the extent of disease at evaluation were collected. These variables included age at diagnosis with pulmonary metastasis, gender, type of primary tumor, the histological subtype, margins,

date of pathological diagnosis, and clinicopathological features, including size of the metastatic lesions and lobes of lungs involved. In addition, other parameters related to the surgical procedure, such as the type of surgery, total number of resected metastatic nodules, and peri-metastasectomy chemotherapy were reviewed and considered for analysis.

Statistical analysisKaplan–Meier analysis was used to estimate survival.

Survival time was defined as the time from the date of first lung metastasectomy until the date of death or last follow-up. The log-rank test was used to compare survival by primary tumor type. Multivariate analysis was implemented using a Cox proportional hazards model to estimate the effect of the following prognostic factors on survival: age at primary tumor diagnosis; primary tumor; location of metastasis in the lung; tumor size; total number of PMs; total number of resected nodules; and use of peri-operative chemotherapy. The results of the Cox regression model are reported with relative risks and 95% confidence intervals (CIs). The analyses were performed using Social Package for Social Sciences (SPSS) version 23. A p value < 0.05 was considered statistically significant.

results

Patient characteristics

Of 42 patients who underwent PM in our institution during the period from 2007 to 2016, 38 patients had PMs from primary colorectal or sarcomatous cancers

Table 1. Basic characteristics of the study subjects

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Survival After Pulmonary Metastasectomy in Sarcoma and Colorectal Primary Cancers, Abdulrahman A. Alghamdi, et. al. Survival After Pulmonary Metastasectomy in Sarcoma and Colorectal Primary Cancers, Abdulrahman A. Alghamdi, et. al.

and were thus included in the study. Table 1 provides the characteristics of the study participants. Seventeen patients (44.7%) had primary colorectal cancer, while 21 patients (55.3%) had sarcoma. Overall, the study group comprised 22 males (57.9%) and 16 females (42.1%). The median age at primary tumor diagnosis was 42 years (range: 12–83 years).

Surgical findings

As shown in Table 2, a total of 25 patients underwent a single metastasectomy, 11 underwent two resections, and two more patients underwent four resections. The majority of patients (52.6%) had more than one nodule to be resected (range: 2–7). The most common site of metastasis was the upper lobe of the right lung (n = 11, 28.9%). Multilobar involvement was present in only one case, and here the metastatic lesions were in the right upper and middle lobes.

All patients with CRC had the adenocarcinoma histological subtype. In contrast, patients with sarcoma had more than one histological subtype, with osteosarcoma being the most common (n = 11, 28.9%). More than half of patients (60.50%) had nodules ≥ 15 mm.

Table 2. Characteristics of resected pulmonary metastatic nodules and peri-operative chemotherapy

figure 1. Kaplan–Meier overall survival curves for colorectal cancer and sarcoma patients who underwent pulmonary metastasectomy

Peri-operative chemotherapy

Neoadjuvant chemotherapy where used in 12 patients (31.6%), while adjuvant chemotherapy was received by 26 patients (68.4%) (Table 2).

Overall survival

By the end of the study period, 11 patients (28.9%) had died. The median follow-up duration after PM was 26 months (range: 0–88 months). Using Kaplan–Meier survival analysis, the 5 year survival was found to be 41% for sarcoma and 89% for colorectal cancer (p value = 0.023) (Figure 1). Further univariate analysis showed that no variable significantly affected the overall survival of patients who had undergone PM with either primary tumor type.

impact of prognostic factors on survival

Using a multivariate Cox proportional hazards model, having primary CRC (hazard ratio )HR( 0.001, 95% CI 0.000–0.156) and tumor size ≥ 15 mm (HR 0.015, 95% CI 0.002–0.802) were associated with prolonged overall survival. Other factors, such as gender, age at diagnosis, site and number of metastases, type of surgery, number of resected nodules, chemotherapy, and radiotherapy showed no significant influence on survival (Table 3).

discussion and Conclusion

The lung is a well-known site for metastasis from various primary tumors, including CRC and sarcoma. It is widely accepted that PM is the only potentially curative choice for these two primary tumors. However, there is

Survival After Pulmonary Metastasectomy in Sarcoma and Colorectal Primary Cancers, Abdulrahman A. Alghamdi, et. al.

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Survival After Pulmonary Metastasectomy in Sarcoma and Colorectal Primary Cancers, Abdulrahman A. Alghamdi, et. al. G. J. O. Issue 28, 2018

a shortage of data showing the long-term effectiveness of this procedure and the prognostic factors affecting outcome. This study aimed to assess the impact of PM on survival in CRC and sarcoma patients treated at PNOC in the period 2007–2016.

Among our patients, the 5-year survival was 89% in those with primary CRC who underwent PM. Several other studies have varied results. One – a systematic review including a total of 2925 patients – had 5-year survival ranging from 27% to 68%. (16) A global retrospective study of 26 institutions reported a 5-year survival of 66%.(17) Al-Ameri et al. also reported 60% 5 year survival for 184 CRC patients who underwent PM. (18) Our high survival rate compared with the literature can be explained by the small sample size and short-term follow-up.

Our patients with primary sarcoma who underwent PM had a 5-year survival of 41%, which is comparable with that reported in different international studies. A systematic review of studies published between 1990 and 2010 showed 5-year survival of 34% and 25% for bone and soft-tissue sarcoma, respectively. (16) Further, Choong et al. have reported a 5-year survival rate of 40% for 274 post-PM, soft-tissue sarcoma patients. (19)

In our study, we found that a larger size of metastatic deposits (≥ 15 mm) was positively associated with longer survival. Larger-scale studies published previously on CRC and sarcoma patients that tested the association of this factor with survival did not find metastatic nodule size to be a significant predictor. (20- 22) There are only a few studies where it was a significant predictor of worse prognosis, and this was when resected nodule size was > 20 mm. (19, 23) The contradiction with our findings might be partially attributed to two factors. First, our sample included patients with more than one primary tumor site, while other studies assessed only metastasectomy of one primary tumor. Second, we use a different cut-off value to stratify nodule size (15 mm versus 20 mm).

In summary, PM for patients with a primary colorectal tumor or sarcoma was shown to have a substantial survival benefit in our sample. We found that having a primary tumor of the colorectal and larger pulmonary metastases were associated with a better outcome. We recommend PM for patients with pulmonary deposits secondary to a primary tumor of colorectum or sarcoma. However, careful selection of candidates is key and needs to be guided by the patient’s individual prognostic factors.

ethical Standards

This project study has been reviewed and approved by the Ethics Committee at King Abdullah International Medical Research Center (KAIMRC), reference number: RYD-16-417780-127304.

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