Jacek Fijuth

Second head and neck cancers following radiation therapy of T1 and T2 cancers of the oral cavity and oropharynx

The risk of second cancer in the head and neck region following definitive radiation therapy was evaluated among 600 patients who were treated for T1 and T2 cancers of the oral cavity and oropharynx at the Henri Mondor hospital between January 1970 and March 1987. Seventy-five patients (12.5%) were managed with external irradiation only, 243 (40.5%) with RT and Iridium 192, and 282 (47%) with Iridium 192 alone. One hundred fifteen patients (19%) developed a second cancer from 3 to 183 months after initial therapy (median: 32 months), including 69 patients (11.5%) in whom the second malignancy was diagnosed in the head and neck region. An increased and constant actuarial risk of development of second head and neck cancer was found (2.7%/year of observation). Univariate analysis showed that age, sex, stage, and modality of the initial treatment did not influence the risk of second head and neck cancer; there was a greater risk of second head and neck malignancy for those patients with soft palate carcinoma (p less than 0.05). Multivariate analysis revealed that the only group of patients who developed a second head and neck cancer more frequently were those who were irradiated with Iridium 192 only (p = 0.0076). There was a trend toward a greater risk of second head and neck malignancy for those with soft palate carcinoma (p = 0.059). Radical treatment of the second head and neck malignancy by surgery and/or re-irradiation was performed for 67% of patients. Patients initially treated by Iridium 192 only could undergo salvage treatment more often than those who previously received external beam radiotherapy (79% vs 53%, p = 0.02). The overall 2-year and 5-year survivals after the diagnosis of the second head and neck cancer were 32% and 10%, respectively.

Results of the whole-brain radiotherapy for patients with brain metastases from lung cancer: The RTOG RPA intra-classes analysis.

We evaluated the overall survival with respect to prognostic factors in patients with brain metastases (BM) from lung cancer in order to assess the RTOG RPA (Recursive Partitioning Analysis) classification value and to perform intra-classes analyses including pretreatment and treatment-related variables. Between 1986 and 1997, 322 consecutive patients with BM from lung cancer were treated with whole-brain radiotherapy. Patients’ distribution according to the RTOG RPA classes was: Class 1 – 13%, Class 2 – 67% and Class 3 – 20%. Prognostic value of the following variables was tested: RTOG RPA classes, performance status, age, extracranial metastases, control of the primary tumour, gender, histology, number of BM and interval from diagnosis to the development of BM. Intra-classes analyses were performed including radiation dose and surgery of BM. Median survival was 4.0 months. Median survival for RTOG RPA classes 1, 2 and 3 were 5.2, 4.0 and 2.5 months, respectively (p = 0.003). Extracranial metastases, performance status, control of the primary and RTOG RPA classes were prognostic for survival. Within class 2 higher radiation dose, female, no extracranial metastases and surgery of BM were related to the improved survival. RTOG RPA classes maintain their prognostic significance for patients with BM from lung cancer not participating in clinical trials.

The analysis of prognostic factors affecting post-radiation acute reaction after conformal radiotherapy for non-small cell lung cancer.

Introduction The aim was to evaluate the risk of acute side effects in the lung after 3-dimensional conformal radiotherapy (3D-CRT) in patients treated for non-small cell lung cancer (NSCLC). An attempt was made to single out clinical factors and factors related to treatment technique which may induce acute post-radiation pneumonitis. Material and methods The analysis concerned 34 consecutive patients who underwent radical radiation therapy for NSCLC. Intensity of early toxicity was evaluated using modified RTOG/EORTC toxicity score. The endpoint for this analysis was the occurrence of radiation pneumonitis of grade 2 or higher. Factors related to treatment techniques were included in the statistical analysis. Results Fifty-three percent of patients included in the study suffered from acute post-radiation pneumonitis. The results of the study revealed the existence of lung tissue sensitivity to low doses of ionizing radiation. The multivariate analysis showed that total lung volume receiving a low dose of 10 Gy increased the risk of post-radiation pneumonitis (p = 0.01). Conclusions Acute post-radiation pneumonitis was a relevant clinical problem in patients who underwent radical radiotherapy for non-small cell lung cancer. The lung volume receiving a dose of 10 Gy was the most important dosimetric factor which influenced the post-radiation acute pneumonitis.

Does obesity hinder radiotherapy in endometrial cancer patients? The implementation of new techniques in adjuvant radiotherapy – focus on obese patients

The increasing incidence of obesity in Poland and its relation to endometrioid endometrial cancer (EEC) is resulting in the increasing necessity of treating obese women. Treatment of an overweight patient with EEC may impede not only the surgical procedures but also radiotherapy, especially external beam radiotherapy (EBRT). The problems arise both during treatment planning and when delivering each fraction due to the difficulty of positioning such a patient – it implies the danger of underdosing targets and overdosing organs at risk. Willingness to use dynamic techniques in radiation oncology has increased for patients with EEC, even those who are obese. During EBRT careful daily verification is necessary for both safety and treatment accuracy. The most accurate method of verification is cone beam computed tomography (CBCT) with soft tissue assessment, although it is time consuming and often requires a radiation oncologist. In order to improve the quality of such treatment, the authors present the practical aspects of planning and treatment itself by means of dynamic techniques in EBRT. The authors indicate the advantages and disadvantages of different types of on-board imaging (OBI) verification images. Considering the scanty amount of literature in this field, it is necessary to conduct further research in order to highlight proper planning and treatment of obese endometrial cancer patients. The review of the literature shows that all centres that wish to use EBRT for gynaecological tumours should develop their own protocols on qualification, planning the treatment and methods of verifying the patients’ positioning.

Solitary brain metastasis of an occult and stable small-cell lung cancer in a schizophrenic patient: a 3-year control.

Small-cell lung cancer is a highly aggressive carcinoma, with poorer prognosis in patients with brain metastases. We present the case of a 49-year-old woman diagnosed with a cerebellar tumour which, following surgery, was revealed to be a metastatic small-cell lung carcinoma. Subsequent CT and PET scanning showed a small, isolated 8 mm nodule in the upper lobe of the right lung. The patient was suffering from schizophrenia and has been treated with clozapine for 17 years. Because of the unusual presentation, there was no therapy given for the primary tumour at the time, and systemic therapy or surgery was discussed. However, 18 months later, the nodule was slightly larger (14 mm), and surgery was performed. On pathology examination, the tumour was presented as a typical small-cell carcinoma. Standard chest irradiation with systemic chemotherapy was given. At the time of writing, 39 months after diagnosis of metastatic small-cell carcinoma, the patient is disease free. However, this case is unusual in that a long-term observation of a small stable primary tumour in the lung took place without any therapy being given. This case strongly supports the thesis that small-cell lung cancer may comprise a heterogeneous group of tumours with different biological properties. The proapoptotic effect of clozapine may be also taken into account.

Highly conformal CT based surface mould brachytherapy for non-melanoma skin cancers of earlobe and nose

Purpose Brachytherapy (BT), due to rapid dose fall off and minor set-up errors, should be superior to external beam radiotherapy (EBRT) for treatment of lesions in difficult locations like nose and earlobe. Evidences in this field are scarce. We describe computed tomography (CT) based surface mould BT for non-melanoma skin cancers (NMSC), and compare its conformity, dose coverage, and tissue sparing ability to EBRT. Material and methods We describe procedure of preparation of surface mould applicator and dosimetry parameters of BT plans, which were implemented in 10 individuals with NMSC of nose and earlobe. We evaluated dose coverage by minimal dose to 90% of planning target volume (PTV) (D90), volumes of PTV receiving 90-150% of prescribed dose (PD) (VPTV90-150), conformal index for 90 and 100% of PD (COIN90, COIN100), dose homogeneity index (DHI), dose nonuniformity ratio (DNR), exposure of organs. Prospectively, we created CT-based photons and electrons plans. We compared conformity (COIN90, COIN100), dose coverage of PTV (D90, VPTV90, VPTV100), volumes of body receiving 10-90% of PD (V10-V90) of EBRT and BT plans. Results We obtained mean BT-DHI = 0.76, BT-DNR = 0.23, EBRT-DHI = 1.26. We observed no significant differences in VPTV90 and D90 between BT and EBRT. Mean BT-VPTV100 (89.4%) was higher than EBRT-VPTV100 (71.2%). Both COIN90 (BT-COIN90 = 0.46 vs. EBRT-COIN90 = 0.21) and COIN100 (BT-COIN100 = 0.52 vs. EBRT-COIN100 = 0.26) were superior for BT plans. We observed more exposure of normal tissues for small doses in BT plans (V10, V20), for high doses in EBRT plans (V70, V90). Conclusions Computed tmography-based surface mould brachytherapy for superficial lesions on irregular surfaces is a highly conformal method with good homogeneity. Brachytherapy is superior to EBRT in those locations in terms of conformity and normal tissue sparing ability in high doses.

Determinants of quality of life in patients with breast cancer undergoing external beam radiotherapy.

Quality of life (QoL) of patients with breast cancer is not dependent only on the presence of the disease, as there is such a multitude of social and clinical factors [1, 2]. However, data on the determinants of QoL in Polish breast cancer patients during the course of radiotherapy are scarce and based on custom-made questionnaires [3], rather than the EORTC QLQ-C30 or QLQ-BR23, which are the tools of choice for such patients [4, 5]. We evaluated breast cancer patients undergoing radiotherapy for treatment-related determinants of QoL and compared them with the intensity of depressive symptoms. A total of 98 women with breast cancer during the standard course of external beam radiotherapy agreed to complete the validated Polish versions 3.0 of EORTC QLQ-C30, QLQ-BR23 (all global, functional and symptom scales) and – at the same time point – the Beck Depression Inventory (BDI) to evaluate the intensity of depressive symptoms. A control group of 127 healthy women referred to the mammography department for screening purposes was evaluated using the BDI. Median age of the study group was 54 (25–75%: 46.7–60.5) years. Breast conserving therapy (BCT) had been performed in 50% of patients. In the breast cancer group, 65% of subjects had undergone some form of chemotherapy and 51% were undergoing hormone therapy. Cronbachs α values for QLQ-C30, QLQ-BR23 and BDI were 0.91, 0.81 and 0.83 respectively, confirming adequate test performance. Median total radiation dose given to the patients was 34 Gy (25–75%: 18–42 Gy), and only affected intensity of nausea/vomiting and constipation subscales (R = 0.25, p = 0.04; R = 0.27, p = 0.03 respectively) of the QLQ-C30 functional scales. No statistically significant correlations were found between the total dose and QLQ-BR23 scales, but the early reactions (RTOG staged ≥ 2 [6]) significantly worsened arm symptom subscale score assessment in QLQ-BR23. Hormonal therapy was not significantly correlated with any of those three questionnaires’ subscores. Previously received chemotherapy impacted neither QLQ-C30 nor BDI results, but it was associated with body image (BRBI) and systemic therapy side effect scores (BRST) (p = 0.02 and p = 0.005). Type of surgical intervention before radiotherapy impacted the field of global health status, resulting in better overall QoL in patients who had undergone BCT (58% (25–75%: 50–67) vs. 50% (25–75%: 42–58); p = 0.0405). BCT was also associated with lower reported intensity of breast symptoms (p = 0.0338) and better perception of future perspectives (BRFU; p = 0.0328). The level of depressive symptoms measured in controls was significantly lower than in cancer patients (median 5 (25–75%: 1–10) vs. 12 (25–75%: 6–17) points; p < 0.0001). BDI scores were correlated negatively and significantly with all functional scales of QLQ-C30 (Spearmans correlation coefficients ranging from –0.36 to –0.46, all p < 0.05) and QLQ-BR23 subscales: BRBI and BRFU (R = –0.47 and –0.51; p < 0.05). In conclusion, radiotherapy itself has a minor influence on QoL of breast cancer patients, although organ-specific complications may significantly impair physical functioning. Other forms of oncological treatment, such as the type of surgical procedure performed, have a much more profound impact on all fields of QoL. Intensity of depressive symptoms is an important determinant of QoL in cancer patients which mandates routine psychological evaluation.

Recurrent Pineocytomalike Papillary Tumor of The Pineal Region: A Case Report and Literature Review

BACKGROUND Papillary tumors of the pineal region (PTPRs) are malignant World Health Organization grade II/III tumors; however, they may perfectly mimic benign tumors (e.g., pineocytomas [World Health Organization grade I]). CASE DESCRIPTION We present a case of a 28-year-old man with a 35-mm tumor of the pineal region. Considering the typical radiological and pathologic presentation, the tumor was first diagnosed as pineocytoma. However, despite first total resection, the tumor recurred after 7 years. The recurrent neoplasm was composed mainly of papillary structures with low-grade atypical cells positive for CKAE1/AE3 and CK18. This categorization led to the final diagnosis of PTPR. The patient underwent adjuvant radiotherapy, which vastly improved his neurologic condition and resulted in significant tumor regression. CONCLUSIONS This case exemplifies that PTPRs can perfectly mimic pineocytomas and simple staining for cytokeratins may warrant correct diagnosis and better treatment.

Hypoxia in prostate cancer

Most human solid tumours contain areas which are less oxygenated than normal tissues. Hypoxia increases resistance to radiotherapy, surgery and chemotherapy, and directly alters the function of tumour cells, stimulating them to de-differentiate and to release angiogenic factors with a view to increasing the blood and oxygen supply. Tumour hypoxia promotes malignant progression and metastasis formation. HIF-1 is a heterodimeric transcription factor composed of regulated HIF-1 α and constitutively expressed HIF-1 β . Tumour-associated activation of HIF-1 α seems to be primarily, however the result of adaptation to oxygen shortage. The presence of the HIF-1 α subunit overexpression has been confirmed in many tumours, in prostate cancer, among others; the role it plays in its progression is yet to be explained. Numerous studies strongly emphasize the importance of evaluating the status of the HIF-1 α transcription factor in predicting the clinical and biochemical recurrence of prostate cancer and its resistance to castration.

Pregnancy-related cervical cancer in the material of the Regional Cancer Centre, Łódź, between 2011 and 2014

Introduction. Pregnancy-related cancer is defined as cancer diagnosed during pregnancy or in the first postpartum year. Cervical cancer affects approximately 1 in 1000 pregnant women and is the most common malignancy affecting pregnancy. We retrospectively analysed the clinical outcome and results of treatment in patients with pregnancy-related cervical cancer. Material and methods. We retrospectively analysed the medical records of nine patients with invasive cervical cancer diagnosed during pregnancy and the postpartum period who had been treated in the Regional Oncological Centre, Łodź, between 2011–2014. Results. Three patients with cervical cancer at stage I were diagnosed between the 14 th and 17 th week of pregnancy afterwards and underwent radical surgery. Two patients with cervical cancer at stage Ib who were diagnosed in the 19 th and 24 th week of gestation decided to continue pregnancy until the 30 th and 32 nd week; then a cesarean section combined with radical surgery was performed. In three patients with inoperative cervical cancer diagnosed between the 26 th and 28 th week of pregnancy, a cesarean section was performed at week 30–32. In one patient cervical cancer at stage IIb was diagnosed during the post-partum period. All patients were treated using intensity-modulated radiotherapy (IMRT) to a total dose of 44 Gy/2Gy, weekly cisplatin (40 mg/m 2 ) concurrent with radiotherapy and brachytherapy. No toxicity was observed. During follow-up, two patients with inoperable cervical cancer were diagnosed with a recurrence 2 and 10 months after treatment, respectively. Conclusions. The management of pregnancy-related cervical cancer is mainly determined by the week of the pregnancy and the stage of the disease at diagnosis, but also by the patient choice. The general condition and follow-up of newborns from pregnancies complicated by cervical cancer are similar to those of newborns arising from non-complicated pregnancies. Treatment toxicity is similar in cases with pregnancy-related cervical cancer and in non-pregnant women with cervical cancer. The major prognostic factor in pregnancy-related cervical cancer remains the stage of the disease at diagnosis.