Malignancies in adult kidney transplant candidates and recipients: current status.

Posttransplant malignancies, particularly recurrent and de novo, in solid organs including kidney transplant recipients (KTRs) are a significant complication associated with substantial mortality, largely attributed to the long-term immunosuppression necessary to maintain allograft tolerance. Older age at transplantation and oncogenic virus infection along with pretransplant malignancies are among the main factors contributing to the risk of cancer in this population. As the mean age of transplant candidates rises, the rate of transplant recipients with pretransplant malignancies also increases. The eligibility criteria for transplantation in patients with prior cancer have recently changed. The overall risk of posttransplant malignancies is at least double after transplantation, including KTRs, relative to the general population, and is most pronounced for skin cancers associated with UV radiation and virally mediated tumors. The risk of renal cell carcinoma is specifically increased in the kidney transplant population. The therapy for cancer in transplant patients is associated with risk of higher toxicity, and graft rejection and/or impairment, which poses a unique challenge in its management. Reduction of immunosuppression and the use of mammalian target of rapamycin inhibitors are common after cancer diagnosis, although optimal immunosuppression for transplant recipients with cancer remains undefined. Suboptimal cancer treatment contributing to a worse prognosis has been reported for malignancies in this population. In this article, we focus on the prevalence and outcomes of posttransplant malignancies, cancer therapy including a short overview of immunotherapy, cancer screening and prevention strategies, and immunosuppression as a cancer risk factor. The 2020/2021 recommendations of the Kidney Disease: Improving Global Outcomes and the American Society of Transplantation for transplant candidates with a history of cancer are presented.

Adjuvant vaginal cuff brachytherapy in surgically treated endometrial carcinoma patients - in view of the recent evidence.

Vaginal cuff brachytherapy is an essential component of adjuvant post-operative therapy in endometrial carcinoma. Brachytherapy boost, as a part of adjuvant pelvic radiotherapy, including concomitant chemoradiotherapy combined with four cycles carboplatin/paclitaxel chemotherapy, is used in early-stage high-risk and advanced stage disease. This strategy is widely accepted and recommended by international guidelines, despite the fact that combined therapy has never been verified in randomized trials. Brachytherapy alone is the adjuvant treatment of choice for many patients with early-stage endometrial cancer, with high-intermediate features, replacing external beam pelvic radiotherapy. It provides equivalent vaginal control with a lower risk of toxicity, and minimal impact on health-related quality of life. Available evidence did not demonstrate the superiority of sole vaginal brachytherapy combined with three cycles of carboplatin/paclitaxel chemotherapy, over the standard pelvic irradiation for patients with early-stage, high-intermediate-, and high-risk endometrial cancer. This article summarized the available evidence on the role of post-operative vaginal cuff brachytherapy in endometrial cancer patients. Additionally, the risk groups definition, some aspects of brachytherapy technique, and the importance of pathological and molecular risk factors for endometrial cancer risk stratification were presented. Furthermore, the role of brachytherapy according to the European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology 2021 guidelines for the management of patients with endometrial carcinoma was presented.

Aromatase inhibitor therapy for endometrial stromal sarcoma - two-centre experience.

OBJECTIVES: Endocrine therapy is the recommended systemic treatment for steroid receptor positive endometrial stromal sarcoma (ESS). There is no current consensus on the optimal hormonal therapy for ESS. The literature offers several reports on advanced/recurrent/metastatic ESS patients treated with progestins, whereas data on the efficacy of aromatase inhibitors are scarce. MATERIAL AND METHODS: We retrospectively identified cases treated for ESS with aromatase inhibitors at our institutions. There were five patients with advanced or unresectable recurrent estrogen, progesterone and androgen receptor-positive ESS, treated with aromatase inhibitors: letrozole or anastrozole (at a daily dose of 2.5 mg and 1 mg, respectively), as first-line endocrine therapy in all but one case treated following progression with megestrol acetate. RESULTS: Disease stabilization was achieved in four cases (80%), including two with long-term progression-free survival for up to 10 years attained under letrozole treatment, and one case after prior progestin treatment. During therapy, no substantial toxicity was observed. CONCLUSIONS: Aromatase inhibitors as first- or second-line endocrine treatment achieve disease control in most steroid receptor positive ESS. Our series of cases is evidence of aromatase inhibitors efficacy as long-term endocrine treatment option for ESS patients.

Systemic therapy for cervical carcinoma - current status.

Two major treatment modalities in cervical cancer are radiation therapy (RT) and surgery. Chemotherapy continues to be the main form of systemic therapy adjunctive to definitive local therapies, and is used for palliation. Platinum-based regimens, administered concurrently with both definitive and postoperative RT, were demonstrated to provide significant survival benefits, whereas the beneficial effect of concurrent chemoradiotherapy in later-stage disease was smaller. The role of chemotherapy in addition to RT in IB1/IIA1 cervical cancer patients not undergoing surgery remains undefined. Likewise, the role of chemotherapy in combination with postoperative RT for patients with intermediate-risk factors for recurrence has not yet been verified. The recent standard for chemoradiotherapy is cisplatin alone administered weekly. Other cisplatin-based or non-cisplatin-based regimens have not been subjected to large clinical studies. The benefits of consolidation chemotherapy after chemoradiation for locally advanced cervical cancer are still undetermined. Neoadjuvant cisplatin-based chemotherapy followed by surgery has shown survival benefits, however its role in the era of chemoradiotherapy remains unclear. The combination of cisplatin and paclitaxel is considered a standard regimen in the palliative setting. There is no standard of care for second-line systemic therapy in advanced cervical cancer. Bevacizumab combined with palliative chemotherapy (cisplatin/paclitaxel or topotecan/paclitaxel) in the first-line treatment for recurrent/metastatic cervical cancer significantly improves overall survival when compared to chemotherapy alone. The role of immunotherapy in cervical cancer remains to be established. The optimal combined modality treatment including systemic therapy for cervical tumors of non-squamous histology remains a matter of debate. Ongoing accumulation of data on genomic and proteomic characteristics provides insight into the molecular heterogeneity of cervical cancer and paves the way for developing molecularly targeted therapies.

Radiation dose to the left anterior descending coronary artery during interstitial pulsed-dose-rate brachytherapy used as a boost in breast cancer patients undergoing organ-sparing treatment.

PURPOSE: To assess dose received by the left anterior descending (LAD) coronary artery during interstitial pulsed-dose-rate brachytherapy (PDR-BT) boost for left-sided breast cancer patients undergoing organ-sparing treatment. MATERIAL AND METHODS: Thirty consecutive pT1-3N0-1M0 breast cancer patients boosted between 2014 and 2015 with 10 Gy/10 pulses/hour PDR-BT following a computed tomography (CT) simulation with the multi-catheter implant were included. The most common localization of primary tumor were upper quadrants. Patients were implanted with rigid tubes following breast conserving surgery and whole breast external beam irradiation (40 Gy/15 or 50 Gy/25 fractions). Computed tomography scans were retrospectively reviewed and LADs were contoured without and with margin of 5 mm (LAD5mm). Standard treatment plan encompassed tumor bed determined by the surgical clips with margin of 2 cm. Dosimetric parameters were extracted from the dose-volume histograms. RESULTS: The mean D90 and V100 were 10.3 Gy (range: 6.6-13.3), and 42.0 cc (range: 15.3-109.3), respectively. The median dose non-uniformity ratio (DNR) was 0.50 (range: 0.27-0.82). The mean doses to LAD and LAD5mm were 1.0 Gy and 0.96 Gy, and maximal doses were 1.57 Gy and 1.99 Gy, respectively. Dose to the 0.1 cc of the LAD and LAD5mm were 1.42 Gy and 1.85 Gy (range: 0.01-4.98 Gy and 0.1-6.89 Gy), respectively. CONCLUSIONS: Interstitial multi-catheter PDR-BT used as a boost for left-sided breast cancer is generally associated with low dose to the LAD. However, higher dose in individual cases may require alternative approaches.

Systemic therapy for endometrial stromal sarcomas: current treatment options.

Uterine endometrial stromal sarcomas including true low-grade endometrial stromal sarcoma (LG-ESS) and high-grade (HG-ESS) or undifferentiated endometrial sarcoma (UES) constitute a group of rare, aggressive malignancies. Most LG-ESSs express steroid receptors. Surgery is the principal primary therapy for endometrial stromal sarcomas and should be considered in all cases. These malignancies are relatively radio- and chemoresistant. Chemotherapy is used in recurrent and advanced HG-ESS and UES. Currently, the combination of gemcitabine and docetaxel is considered the most effective regimen, but at the expense of substantial toxicity. In steroid receptor positive advanced LG-ESS hormonal therapy, mainly with progestins, allows in some patients for a long-term survival. Aromatase inhibitors seem to be equally effective as first- and subsequent-line of treatment, and are well tolerated. The role of molecular-targeted therapies in endometrial stromal sarcomas remains to be established.

Endocrine disrupting chemicals as potential risk factor for estrogen-dependent cancers.

Civilization, industrialization, and urbanization create an environment where humans are continuously exposed to endocrine disrupting chemicals (EDCs). Some of breast cancers and endometrial cancer, which are the most common female malignant neoplasms, are estrogen-dependent tumors. Prolonged exposure to estrogens or substances with estrogenic properties may be a risk factor for their development. This paper aimed to discuss the potential adverse effect of EDCs on human health, including the role of EDCs in hormone-dependent carcinogenesis. A review of literature regarding the sources of environmental exposure to EDCs and molecular mechanisms of their action was performed. We analyzed the possible mechanisms of how these substances alter the function of the endocrine system, resulting in adverse health effects. Hundreds of substances with endocrine disrupting potential have been identified in our environment. There is accumulating evidence linking exposure to EDCs with the development of mammary and endometrial cancer. By interacting with steroid receptors, EDCs can impact the cellular processes potentially leading to carcinogenesis. There are also data showing the effect of EDCs on immune dysfunction. During lifespan, people are usually exposed to a mixture of various EDCs, which complicates the assessment of individual substances or compounds implicated in cancer development. As the prevalence of hormone-dependent tumors among women continues to increase, their successful prevention is of human benefit. Institutions representing medicine, science, industry, and governments should develop joint strategies to decrease exposure to EDC, and thus to reduce the risk of hormonedependent tumors in women.

Pulsed-dose-rate peri-operative brachytherapy as an interstitial boost in organ-sparing treatment of breast cancer.

PURPOSE: To evaluate peri-operative multicatheter interstitial pulsed-dose-rate brachytherapy (PDR-BT) with an intra-operative catheter placement to boost the tumor excision site in breast cancer patients treated conservatively. MATERIAL AND METHODS: Between May 2002 and October 2008, 96 consecutive T1-3N0-2M0 breast cancer patients underwent breast-conserving therapy (BCT) including peri-operative PDR-BT boost, followed by whole breast external beam radiotherapy (WBRT). The BT dose of 15 Gy (1 Gy/pulse/h) was given on the following day after surgery. RESULTS: No increased bleeding or delayed wound healing related to the implants were observed. The only side effects included one case of temporary peri-operative breast infection and 3 cases of fat necrosis, both early and late. In 11 patients (11.4%), subsequent WBRT was omitted owing to the final pathology findings. These included eight patients who underwent mastectomy due to multiple adverse prognostic pathological features, one case of lobular carcinoma in situ, and two cases with no malignant tumor. With a median follow-up of 12 years (range: 7-14 years), among 85 patients who completed BCT, there was one ipsilateral breast tumor and one locoregional nodal recurrence. Six patients developed distant metastases and one was diagnosed with angiosarcoma within irradiated breast. The actuarial 5- and 10-year disease free survival was 90% (95% CI: 84-96%) and 87% (95% CI: 80-94%), respectively, for the patients with invasive breast cancer, and 91% (95% CI: 84-97%) and 89% (95% CI: 82-96%), respectively, for patients who completed BCT. Good cosmetic outcome by self-assessment was achieved in 58 out of 64 (91%) evaluable patients. CONCLUSIONS: Peri-operative PDR-BT boost with intra-operative tube placement followed by EBRT is feasible and devoid of considerable toxicity, and provides excellent long-term local control. However, this strategy necessitates careful patient selection and histological confirmation of primary diagnosis.

Castleman's disease mimicking lymph node metastases in a young woman with laryngeal cancer.

Laryngeal cancer occurs rarely in adolescents and young people. Castleman's disease is a rare lymphoproliferative disorder of uncertain etiopathogenesis and heterogeneous clinicopathological forms. Involved lymph nodes and extranodal lesions in the course of Castleman's disease may mimic malignant involvement. We report a case of an 18-year-old woman with T2N0M0 laryngeal glottis cancer treated with definitive radiotherapy. During the irradiation, the patient underwent an excision of incidentally discovered left-sided enlarged cervical lymph nodes located outside the irradiated area. Coincidental hyaline vascular type of Castleman's disease was diagnosed. During six-year follow-up she has been free of cancer relapse and Castleman's disease symptoms.

[Chemosensitivity testing in ovarian cancer--prospects for the future]. / Metody okreslajace chemiowrazliwosc komórek raka jajnika in vitro--perspektywy na przyszlosc.

Individualization of treatment on the basis of in vitro chemosensitivity testing constitutes one of the aims of contemporary oncology Although previous studies report advantages resulting from chemosensitivity laboratory tests, the issue remains an area of interest. The aim of this study was to discuss chemosensitivity assay methods of ovarian cancer cells. ATP-TCA (ATP-based tumor chemosensitivity assay) is the most investigated chemosensitivity test in ovarian cancer with well-documented efficacy Potentially it is possible to use the xCELLigence system to evaluate chemosensitivity of ovarian cancer cells by measuring their colony volume but application of this method remains in the experimental phase. Optimization of ovarian cancer treatment would improve chemotherapy results, thus increasing the overall survival, improving the quality of patient life, decreasing chemotherapy-related toxicity and resulting in economic benefits owing to better drug use.

Pulsed dose rate brachytherapy of lip cancer.

PURPOSE: To present our experience with pulsed dose rate brachytherapy (PDR BT) of lip cancer. MATERIAL AND METHODS: The study group included 32 T1-4N0M0 lip cancer patients with a median age of 71 years (ranged 41-87 years), treated with interstitial PDR BT to the planned total dose of 60-70 Gy; 1 Gy/pulse, pulses repeated every hour a day. There were 26 untreated patients, and six patients after previous surgery including five implanted at the time of cancer relapse. RESULTS: PDR BT was delivered over few days and was well tolerated. After therapy, all patients experienced temporary, usually mild, acute mucositis. Late severe (Grade 3) mucositis of oral vestibule mucosa occurred in one case. Among 31 patients who completed the therapy, local control was achieved in 29 (93.5%). One patient with reccurrent upper lip T2 tumor was susccessfully salvaged surgically, another one died due to persisted T3 lip tumor with lymph node metastases. Overall, four patients developed neck nodal cancer relapse and two - distant metastases. The 5-year local control, and all-cause overall survival probabilities are 94% and 73%, respectively. Good/excellent cosmetic and functional outcome was obtained in all but two patients. CONCLUSIONS: PDR at the dose of 1 Gy/pulse is effective and well tolerated BT technique in treating lip cancer patients.

The role of hormonal factors and endocrine therapy in ovarian cancer.

The efficacy of the second-line chemotherapy commonly used in both relapsed ovarian cancer patients and those with primary treatment failure remains unsatisfactory. This therapy has a small effect on survival, whereas associated toxicity may diminish the patient's quality of life. Hormonal factors play a role in ovarian tumorigenesis, and inhibition of the stimulating effects of estrogens may exert a clinical benefit. The role of hormonal therapy as a palliative therapeutic alternative for ovarian cancer remains undetermined. This modality may result in long-term stabilization of disease in individual patients and less frequently in tumor remission. In this article the role of hormonal factors and recent literature of various forms of hormonal therapy for ovarian cancer are presented.

Continuous 7-days-a-week external beam irradiation in locally advanced cervical cancer: final results of the Phase I/II study.

PURPOSE: To evaluate the feasibility and efficacy of definitive continuous 7-days-a-week pelvic irradiation without breaks between external beam radiotherapy and brachytherapy in locally advanced cervical cancer. METHODS AND MATERIALS: Between November 1998 and December 1999, 30 patients with International Federation of Obstetrics and Gynecology Stage IIB or IIIB cervical cancer were included in a prospective Phase I/II study of continuous 7-days-a-week pelvic irradiation, to the total Manchester point B dose of 40.0-57.6 Gy. The first 13 patients (Group A) were given a daily tumor dose of 1.6 Gy, and the remaining 17 patients (Group B) were given 1.8 Gy. One or two immediate brachytherapy applications (point A dose 10-20 Gy, each) were performed in 28 cases. RESULTS: Two patients did not complete the irradiation because of apparent early progression of disease during the irradiation. Eleven of the 28 evaluable patients (39%; 45% and 35% in Groups A and B, respectively) completed their treatment within the prescribed overall treatment time. Acute toxicity (including severe European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 and 4 effects in 40%) was experienced by 83% of patients and resulted in unplanned treatment interruptions in 40% of all patients (31% and 47% of patients in Groups A and B, respectively). Severe intestinal side effects occurred in 31% and 41% of Patients in Groups A and B, respectively (p = 0.71). The 5-year overall survival probability was 33%. Cancer recurrence occurred in 63% of patients: 20% inside and 57% outside the pelvis. Cumulative incidence of late severe bowel and urinary bladder toxicity at 24 months was 15%. CONCLUSION: Continuous irradiation in locally advanced cervical cancer is associated with a high incidence of severe acute toxicity, resulting in unplanned treatment interruptions. Late severe effects and survival after continuous radiotherapy do not substantially differ from those obtained with conventionally fractionated radiotherapy.

[Uterine carcinosarcoma]. / Miesakorak trzonu macicy.

Uterine carcinosarcoma is a rare, metaplastic subtype of endometrial cancer comprised of two distinct malignant components - epithelial and mesenchymal, with phenotypic features. This tumor shows very aggressive behavior including both local recurrence and distant metastases. Surgery consisting of total hysterectomy bilateral salpingo-oophorectomy and dissection of pelvic and para-aortic lymph node, with detailed examination of the entire abdominopelvic cavity and maximal cytoreduction of the lesions, is the principal treatment. The optimal postoperative therapy has not been determined, and is individualized. In a randomized trial a postoperative radiotherapy was shown to improve local control but no survival benefit. High rate of distant metastases suggests a potential role of the systemic therapy However the benefit of postoperative chemotherapy in high-risk patients has not been confirmed in randomized studies. This method, in addition to palliative radiotherapy and surgery is used in recurrent and advanced disease. Currently chemotherapy including the combination of paclitaxel with ifosfamide or carboplatin is considered the most effective regimen, with the latter having a better toxicity profile.

Paclitaxel and cisplatin chemotherapy for ovarian cancer during pregnancy: case report and review of the literature.

The safety of chemotherapy during pregnancy is debatable. We present a case of advanced ovarian cancer, diagnosed at week 28 of gestational age, treated with 2 cycles of paclitaxel/cisplatin (TC) chemotherapy during pregnancy, with no serious toxicity. At week 34, the patient underwent a caesarean section and delivered a healthy girl. Four additional cycles of TC were administered. Three months after completing chemotherapy, the patient developed abdominal progression and subsequently a huge metastatic cystic mass in the brain. Despite subsequent therapies, the patient died of progressive disease 35 months after the diagnosis. The infant had normal growth and development by 73 months of her age. This is another reported case of ovarian cancer diagnosed during the second trimester of the pregnancy treated with TC chemotherapy without apparent teratogenic effect.

Comparison of two techniques of interstitial pulsed dose rate boost brachytherapy in conservative treatment of breast cancer.

PURPOSE: The aim of this work is to compare selected parameters of implants and natural dose volume histograms for two techniques of interstitial pulsed dose rate brachytherapy (PDR BT) as a boost to the tumour bed in breast-conserving therapy (BCT). MATERIAL AND METHODS: Data of T1-3N0-2M0 breast cancer patients who underwent BCT with BT boost between 05.2002 and 12.2008 were analysed. Ninety two patients were implanted with rigid tubes after breast irradiation (group A) and 96 had a peri-operative BT with an intra-operative flexible tube placement and subsequent whole breast radiotherapy (group B). In both groups PDR BT of 15 Gy (1 Gy/pulse/h) was administered based on Paris system rules, and volume optimization using BT planning system PLATO. RESULTS: Three-plane implant was used in 62% and 8% of patients in group A and B, respectively, and two-plane implant in 38% of group A and in 84% of group B, with a median of 11 and 9 tubes respectively. The average volume for the prescribed dose (V100) was 42.0 ± 25.4 cc (group A) and 34.1 ± 19.7 cc (group B), respectively (p = 0.017). The individual V50 and V200 were similar. Quality index (QI) was not impacted by the technique of BT (mean QI was 1.80 ± 0.10 and 1.75 ± 0.46 for the groups A and B, respectively). Uniformity index (UI) in respective groups was 1.60 ± 0.10 and 1.52 ± 0.21 (p = 0.001). CONCLUSIONS: Implant volume encompassed by prescribed dose was significantly lower with intra-operative plastic tubes placement. In respect to the QI, these two BT techniques were comparable. The target volume coverage by the dose distribution as defined by UI was better for rigid tubes.

Preliminary report of pulsed dose rate brachytherapy in head-and-neck cancer.

PURPOSE: To assess the feasibility and acute/delayed toxicity of pulsed-dose-rate brachytherapy (PDR BT) in head-and-neck tumors. PATIENTS AND METHODS: 45 head and neck cancer patients underwent interstitial or contact PDR BT at a dose of 10.2-70 Gy (median, 70 Gy) and 0.6 or 1.0 Gy/pulse/h. 42 patients were administered BT as part of their curative treatment; 32 of them had sole BT. Three reirradiated patients with recurrent tumor had palliative BT. RESULTS: PDR BT was well tolerated. Intense bleeding was the only complication associated with catheter removal from the tongue and bucca. 44 patients who completed BT experienced acute mucositis. Grade 3 toxicity of skin and oral mucosa occurred in three (6.8%) and six patients (13.6%), respectively. At a median follow-up of 22 months (range, 2-67 months), late serious toxicity (grade 4, for soft tissue and bone) was seen in seven patients (15.9%). Among the parameters analyzed, only dental care performed before BT had a significant impact on mucosal side effects. Acute severe mucositis was observed in 23% of patients without dental care compared to 0% of those with dental care (p=0.044). Late severe mucositis occurred in 17.7% and 26.9% of the respective patients (p=0.035), overall in 23%. The larger the volume encompassed by the reference isodose, the more late (p=0.004) mucosal reactions were observed. CONCLUSION: PDR BT continued over a few days is a feasible and safe approach in head-and-neck tumors; however, it is accompanied by some toxicity. Dental care should precede isotope application.

Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy.

The prognostic impact of pretreatment hemoglobin (Hb) level and its changes during definitive radiotherapy was evaluated by univariate and multivariate analysis in the group of 453 FIGO IB-IIIB cervical cancer patients. Pretreatment anemia (Hb < 12 g/dl) was present in 148 patients (33%), and anemia at the end of irradiation in 48%; in 64% Hb level declined during therapy. Median overall survival in patients with initial Hb >or=12 g/dl was 66 months compared to 22 months in those with lower baseline Hb levels (p = 0.0001). This difference was mainly due to increased risk of distant spread in anemic patients (40% compared to 25% in subjects with pretreatment Hb >or=12 g/dl; p = 0.001). Baseline Hb >or=12 g/dl was also associated with longer disease-free survival and improved local control. Declining Hb level during radiotherapy predicted for impaired 5-year disease-free survival and local control probability. In multivariate analysis, low pretreatment Hb level remained associated with worse overall and disease-free survival, whereas adverse impact of declining Hb level on outcome was not observed. With regard to other clinical factors, stage and tumor extension (uni- or bilateral parametrium involvement for Stage III) were the only independent determinants of prognosis.

EPR/alanine dosimetry in LDR brachytherapy--a feasibility study.

In this study, we present the results of in vivo dosimetry, using electron paramagnetic resonance in l-alanine, performed on 13 patients treated for gynaecological cancers. The doses from (137)Cs (12 samples) and (192)Ir (one sample) brachytherapy sources were determined inside vagina. The detectors had a form of small cellulose capsules tightly filled with crystalline alanine. The positions of the detectors were reconstructed from two orthogonal radiographs. The planned doses were calculated with a computer planning system (PLATO, Nucletron). The relative deviations between planned and measured doses ranged from -23 to +14%. The mean deviation from the prescribed dose was relatively low (-5%) with SD of 10%. The main sources of differences between the measured and calculated doses were attributed to uncertainty in the determination of the detector position inside the patient's body and to uncontrolled changes in the detector position during the treatment.