Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy.

BACKGROUND: Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory. METHODS: In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores. RESULTS: A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis. CONCLUSION: Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Searching for answers: Cancer care during the COVID pandemic.

The unprecedented novel coronavirus disease pandemic has wreaked havoc on healthcare systems worldwide and raised myriads of questions. The delivery of cancer care is an essential service that cannot take a backseat, even amid a global pandemic. Oncology involves the disciplines of surgical oncology, radiotherapy, chemotherapy, and palliative care which are all affected, including the possible impact of the pandemic on the mental health of patients and healthcare workers alike. This commentary attempted to review these questions in light of the best available evidence. The delivery of cancer care is generally safe when routine safety precautions are followed, and decisions are based on rational scheduling and logistical prioritisation. The impact on the mental health is profound that needs to be addressed with adequate avenues. Teleoncology is a reasonable alternative, whenever applicable. Evidence-based decision making should be the standard of care, and multidisciplinary management decisions are as indispensable as ever.

Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center?

BACKGROUND: Role of hypofractionated radiotherapy (HFRT) in early breast cancer is established; comparatively, there are limited data for HFRT in locally advanced breast cancer (LABC). We report the impact of HFRT in unselected breast cancer patients in comparison with historically treated patients with conventional fractionated radiotherapy (CFRT). PATIENTS AND METHODS: Records of 463 breast cancer patients treated between January 09 and July 13 with CFRT (50 Gy/25 fr) or HFRT (42.4 Gy in 16 fractions or 40 Gy in 15 fractions) in two sequential periods were retrospectively reviewed. The analysis was done in August 2018. The primary endpoint was to compare the differences in locoregional recurrence rate. RESULTS: Of the 463 patients, 209 received CFRT and 254 received HFRT. The median age was 48 years (interquartile range: 40-56), premenopausal (CFRT: 23% vs. HFRT 39%, P = 0.005). The most common pathology was infiltrating ductal carcinoma (81%) with Grade III tumors (45%), estrogen receptor (+) was seen in 44%, triple-negative breast cancer in 34%, and Her2Neu (3+) were seen in 27%. Two hundred and fifty-four patients (54.5%) had undergone breast-conserving surgery (BCS) and 209 patients (45%) modified radical mastectomy (MRM). Nodal radiotherapy was delivered in 76% versus 64% in patients receiving CFRT versus HFRT, respectively (P = 0.005). With a median follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4 years#39; actuarial local recurrence-free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37). The mean estimated LRFS (local relapse-free survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3). CONCLUSIONS: The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to CFRT.

Objective and subjective assessment of xerostomia in patients of locally advanced head-and-neck cancers treated by intensity-modulated radiotherapy.

BACKGROUND: Parotid-sparing intensity-modulated radiotherapy (IMRT) effectively reduces xerostomia in head-and-neck cancer (HNC). Changes in the salivary output at 1 year were studied and correlation with quality of life (QOL) changes in patients of locally advanced HNC (LAHNC) was drawn. MATERIALS AND METHODS: Between October 2009 and October 2011, 20 patients of LAHNC were treated with IMRT using simultaneous integrated boost technique. High-risk clinical target volume (CTV) was given a dose of 66 Gy/30 fr, intermediate-risk CTV 60 Gy/30 fr, and low-risk CTV 54 Gy/30 fr. The saliva flow rate was estimated for 5 min at rest (unstimulated) and after using lemon drops (stimulated) for the next 5 min, at baseline (pretreatment), and 3, 6, and 12 months following treatment. Evaluation of patients' perception of dry mouth was done using EORTC-QLQ-C30 and HN35 questionnaires at the same time points. RESULTS: Baseline unstimulated and stimulated salivary flow rates were 0.659 ml/min and 1.69 ml/min, respectively. At 3 months, a significant reduction in unstimulated (0.346 ml/min) and stimulated (0.80 ml/min) flow rate was observed. Unstimulated flow rate continued to decrease further till 6 months (0.295 ml/min), but slight improvement was seen in stimulated flow rate (0.91 ml/min). At 12 months, minimal recovery was observed in both unstimulated (0.362 ml/min) and stimulated flow rates (1.09 ml/min). EORTC-QOL questionnaire mean scores for dryness and stickiness of saliva were 10 and 15 at baseline and increased to 36 and 25, respectively, at 3 months. At 6 months, symptom score for dryness further increased to 45 and then decreased to 33 at 12 months. Stickiness score remained static from 3 to 12 months. Salivary flow rate correlated well with dry mouth (P < 0.05) but not with the perception of sticky saliva (P = 0.82) at 6 months and beyond. CONCLUSIONS: Both salivary flow rate and xerostomia-related questions worsened at 3 months even with IMRT and showed a similar pattern of recovery.

Initial Experience of Head and Neck Cancer Patients Treated in an Oncologist Led Palliative Cancer Care Clinic at a Tertiary Cancer Care Center in Uttar Pradesh: Is the Initiative of a Full-fledged Palliative Care for Cancer Patients Justified.

INTRODUCTION: Poor socioeconomic status and illiteracy attribute to the advanced presentation of head and neck cancer (HNC) patients in India and are candidates for palliation in our setup. We set up a palliative cancer care clinic (PCCC), and an audit of initial 153 HNC patients is presented. AIMS AND OBJECTIVES: To assess the impact of palliative cancer care services. METHODOLOGY: Data of advanced HNC patients suited for palliation were collected to document demography, symptomatology, cancer treatment, and supportive care. RESULTS: One hundred and fifty-three patients were seen during January 2013 to March 2015 in the PCCC. Seventy-two (47%) referral cases were due to disease progression and 81 (53%) due to de novo advanced cases. Median follow-up for this group was 5.3 months. Ninety (59%) cases needed some degree of assistance for their normal activities. Sixty-seven (44%) patients belonged to poor socioeconomic status and 65 (43%) were educated up to equivalent of high school. One hundred and thirty-five (88%) patients had an adequate family support. Pain was the most common presenting symptom in 134 (87%) cases with adequate relief in 112 (84%) patients with another 13 (09%) could not be assessed. Overall median duration of symptoms was 6 months. Cancer-directed therapy was used in 143 (93%) patients. Near the end of life in 47 (73%) out of 63 documented cases, caregivers were psychologically prepared for the inevitable. CONCLUSION: The role of palliative care team in alleviating physical, psychosocial, and emotional issues of patient and family members was significant. PCCC seems to be a feasible working model in our setup.

Long term results of comparison of concurrent low-dose daily cisplatin versus the standard weekly cisplatin with six fractions per week radiotherapy in locally advanced head neck cancer.

AIM AND OBJECTIVE: Weekly administration of cisplatin (cis-diamminedichloroplatinum [CDDP]) appears more feasible and substantially more popular than the 3 weekly schedules due to better compliance. Different concurrent cisplatin schedules have been attempted including a daily schedule. We did a comparison of two consecutive single arm studies, i.e., use of weekly cisplatin versus daily cisplatin when used with concurrently with a moderately accelerated radiotherapy (RT) schedule. PATIENTS AND METHODS: Two prospective feasibility, safety and efficacy studies were carried out consecutively within the department. The weekly CDDP study was done from August 2003 to August 2005 and daily CDDP study was conducted from November 2005 to June 2007. Both studies included locally advanced stage III and IV squamous cell carcinoma of the head and neck region with RT dose of 70 Gy. Concurrent single-agent cisplatin was administered weekly (35 mg/m(2)) in the first and daily (6 mg/m(2)) in the second study. RESULTS: Weekly cisplatin study had 68 and daily CDDP study had 52 patients. The median follow-up in the two studies was 93 and 63 months, respectively. Compliance in the two studies was comparable. Acute Grade III/IV mucositis and dysphagia were significantly higher in weekly cisplatin study. Late Grade II/III toxicities such as xerostomia, dysphagia, ototoxicity and nephrotoxicity were similar. The 5 years locoregional control was 18% and 25% and 5 years overall survival rate was 32% and 31% in weekly and daily cisplatin studies, respectively. CONCLUSIONS: Modest acceleration along with either weekly or daily cisplatin, whichever is possible in one's setup, is do-able, provided due attention is paid to patient selection and supportive care.

Is aspiration as detected on pretreatment video fluorography, a harbinger of poor quality of life and early mortality in cancers of the upper aerodigestive tract treated with radiotherapy?

BACKGROUND: Patients with cancers of the upper aerodigestive tract (head and neck cancer (HNC)) tend to aspirate, either due to disease or treatment. The association of aspiration (documented on video fluorography (VFG)) with quality of life (QOL) and unexpected mortality was studied prospectively in patients treated with simultaneous integrated boost technique of intensity-modulated radiotherapy (SIB-IMRT). MATERIALS AND METHODS: Moderately advanced (stage III/IV) HNC were treated by SIB-IMRT delivering 66 Gy/30 fr, 60 Gy/30 fr, and 54 Gy/30 fr to high, intermediate, and low risk volumes, respectively. They underwent serial VFG and QOL assessments (Quality of Life Questionnaire-Core 30 (QLQ-C30) and head and neck-35 (HN35) European Organisation for Research and Treatment of Cancer (EORTC) tools) at 0, 3, and 6 months. Pharyngeal musculature (PM) was additionally delineated on planning computed tomography (CT) scans as potential organs at risk (OARs). RESULTS: Between November 2009 and May 2011, 20 HNC were treated as per protocol. All patients were fit (Karnofsky performance status (KPS) ≥ 80). Based on VFG findings, seven patients (4/9 oropharynx and 3/11 laryngopharynx) were grouped as aspirators (A) and remaining 13 as non-aspirators (NA). The QOL study showed that pretreatment coughing and swallowing difficulties were greater in group A versus NA and remained persistently higher. In group A, deaths attributable to aspiration were seen in 3/7 patients, while none occurred in the NA group (Fisher's exact P = 0.03). The mean PM dose was 60 Gy in both the groups and mean V60 was similar at 69 and 67% in A and NA groups, respectively. CONCLUSIONS: VFG helps identify patients who aspirate and are at risk of premature death due to its complications, alerting caregivers to direct attention appropriately.